Pioglitazone, a PPARγ agonist, inhibits growth and invasion of human hepatocellular carcinoma via blockade of the rage signaling
Abstract
Pioglitazone (PGZ), a synthetic PPARγ ligand, is known to have anti‐tumor activity. However, it is unclear how it acts against hepatocellular carcinoma (HCC). We hypothesized that the pathological receptor for advanced glycation end products (RAGE) is involved in the PGZ anti‐tumor process. To test this notion, human primary HCC tissues and corresponding adjacent non‐cancerous tissues (ANCT) from 75 consecutive cases were analyzed. The expression and clinical significance of RAGE was assessed by immunohistochemical assay through tissue microarray. After HCC cells were pretreated with different concentrations of PGZ, cell proliferation, apoptosis, cell invasion, and cell cycle distribution were evaluated by multiple assays. The results showed that, the positive expression of RAGE was significantly higher in HCC tissues than in ANCT (66.7% vs. 36.0%, P < 0.001), and was closely associated with pathological staging (P = 0.014) and lymph‐vascular space invasion (P = 0.003). Moreover, PGZ inhibited proliferative activity and invasive potential, and induced apoptosis and cell cycle arrest in HCC cells resulting in increased expression of PPARγ and decreased expression of RAGE, NF‐κB, HMGB1, p38MAPK, Ki‐67, MMP‐2, and CyclinD1. Furthermore, knockdown of RAGE or NF‐κB by siRNA effectively suppressed cell proliferation and invasion, and mediated the inhibitory effects of PGZ in HCC cells. Taken together, our findings suggest that, RAGE is overexpressed in human HCC tissues, and is closely associated with the pathological staging and tumor invasion of HCC. In addition, PGZ as a PPARγ agonist may inhibit growth and invasion of HCC cells via blockade of the RAGE signaling. © 2014 Wiley Periodicals, Inc.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
AGEs and RAGE play an important role in promoting NAFLD, NASH, fibrosis/cirrhosis, and HCC pathogenesis.
“These results suggest an important role for AGEs and RAGE in promoting NAFLD, NASH, fibrosis/cirrhosis, and HCC pathogenesis129–131.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [131]
RAGE amounts are increased in HCC liver compared with hepatitis and healthy liver, and serum AGE amounts are higher in HCC than in NASH and healthy liver specimens.
“Increased amounts of RAGE are also observed in the liver of hepatocellular carcinoma (HCC), and its level is significantly greater than it is liver affected by hepatitis and healthy liver specimens.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [131]
In HCC, AGE-RAGE interaction is associated with angiogenesis and tumor proliferation and invasion, which are ameliorated by RAGE inhibition.
“In HCC, the AGE-RAGE interaction is associated with angiogenesis and tumor proliferation and invasion, which are ameliorated by RAGE inhibition.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [131]
Soluble RAGE, inhibitors of the RAGE signaling pathway, neutralizing antibodies against RAGE or AA-AGE adduct, and other AGE-degrading compounds have been reported to decrease AGE adduct formation.
“Furthermore, soluble RAGE119,200, inhibitors of the RAGE signaling pathway130,131, neutralizing antibodies against RAGE57 or AA-AGE adduct199, and other AGE-degrading compound(s), such as pyridoxamine and ALT-711200, lipoic acid291, synthetic compounds OPB-9195292, and nitrothiadiazolo[3,2-α]pyrimidines293, have been reported to decrease AGE adduct formation.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [131]
Cites
2 retracted
Zhu, J.-S. (2012) · Oncology Reports · doi:10.3892/or.2012.1623 · Cited by 34 · see citing works
RetractedZhang, J., Zhu, J., Zhou, Z., Chen, W., & Chen, N. (2016) · Oncology Reports · doi:10.3892/or.2016.5181 · Cited by 13 · see citing works
RetractedJemal, A., Bray, F., Ferlay, J., Ward, E., & Forman, D. (2011) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.20107 · Cited by 54,708 · see citing works
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008
Ferlay, J., Shin, H., Bray, F., Forman, D., Mathers, C. D., & Parkin, D. M. (2010) · International Journal of Cancer · doi:10.1002/ijc.25516 · Cited by 21,271 · see citing works
Kang, R., Tang, D., Schapiro, N. E., Livesey, K. M., Farkas, A. M., Loughran, P., Bierhaus, A., Lotze, M. T., & Zeh, H. J. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.149 · Cited by 333 · see citing works
Ueda, J., Kajita, M., Suenaga, N., Fujii, K., & Seiki, M. (2003) · Oncogene · doi:10.1038/sj.onc.1206962 · Cited by 135 · see citing works
He, Q., You, H., Li, X., Liu, T., Wang, P., & Wang, B.-E. (2012) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2012.13.4.1365 · Cited by 113 · see citing works
The role of HMGB1-RAGE axis in migration and invasion of hepatocellular carcinoma cell lines
Chen, R.-C., Yi, P.-P., Zhou, R.-R., Xiao, M.-F., Huang, Z.-B., Tang, D., Huang, Y., & Fan, X. (2014) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-014-1978-6 · Cited by 109 · see citing works
Mizumoto, S., Takahashi, J. A., & Sugahara, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.313437 · Cited by 99 · see citing works
Grommes, C., Landreth, G. E., Sastre, M., Beck, M., Feinstein, D. L., Jacobs, A. H., Schlegel, U. S., & Heneka, M. T. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.022194 · Cited by 98 · see citing works
Rumi, M. A. K., Sato, H., Ishihara, S., Kawashima, K., Hamamoto, S., Kazumori, H., Okuyama, T., Fukuda, R., Nagasue, N., & Kinoshita, Y. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.1821 · Cited by 89 · see citing works
Activation of PPARγ in Myeloid Cells Promotes Lung Cancer Progression and Metastasis
Li, H. Y., Sorenson, A. L., Poczobutt, J. M., Amin, J., Joyal, T., Sullivan, T., Crossno, J. T., Weiser-Evans, M. C. M., & Nemenoff, R. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028133 · Cited by 75 · see citing works
Yoshizawa, K., Cioca, D., Kawa, S., Tanaka, E., & Kiyosawa, K. (2002) · Cancer · doi:10.1002/cncr.10906 · Cited by 73 · see citing works
Jiao, L., Taylor, P. R., Weinstein, S. J., Graubard, B. I., Virtamo, J. R. K., Albanes, D., & Stolzenberg‐Solomon, R. Z. (2011) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-11-0066 · Cited by 71 · see citing works
Jiao, L., Weinstein, S. J., Albanes, D., Taylor, P. R., Graubard, B. I., Virtamo, J. R. K., & Stolzenberg‐Solomon, R. Z. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2573 · Cited by 70 · see citing works
Elangovan, I., Thirugnanam, S., Chen, A., Zheng, G., Bosland, M. C., Kajdacsy‐Balla, A., & Munirathinam, G. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.12.060 · Cited by 64 · see citing works
Takino, J. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i15.1781 · Cited by 64 · see citing works
Yaser, A.-M., Huang, Y., Zhou, R.-R., Hu, G.-S., Xiao, M.-F., Huang, Z.-B., Duan, C.-J., Tian, W., Tang, D., & Fan, X. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13055982 · Cited by 63 · see citing works
Motomura, W., Takahashi, N., Nagamine, M., Sawamukai, M., Tanno, S., Kohgo, Y., & Okumura, T. (2003) · International Journal of Cancer · doi:10.1002/ijc.11561 · Cited by 61 · see citing works
Liang, H., Zhong, Y., Zhou, S., & Peng, L. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.08.028 · Cited by 60 · see citing works
Rage signalling promotes intestinal tumourigenesis
Heijmans, J., Büller, N. V. J. A., Hoff, E., Dihal, A. A., van der Poll, T., van Zoelen, M. A. D., Bierhaus, A., Biemond, I., Hardwick, J. C. H., Hommes, D. W., et al. (2012) · Oncogene · doi:10.1038/onc.2012.119 · Cited by 59 · see citing works
Shigeto, T., Yokoyama, Y., Xin, B., & Mizunuma, H. (2007) · Oncology Reports · doi:10.3892/or.18.4.833 · Cited by 58 · see citing works
Lin, L., Zhong, K., Sun, Z., Wu, G., & Ding, G. (2011) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-011-1067-0 · Cited by 57 · see citing works
Dobson, M. E., Diallo, E. M., Grachtchouk, V., Yu, J., Colby, L. A., Wilkinson, J. E., Giordano, T. J., & Koenig, R. J. (2011) · Endocrinology · doi:10.1210/en.2011-1178 · Cited by 57 · see citing works
Al-Alem, L., Southard, R. C., Kilgore, M. W., & Curry, T. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016179 · Cited by 53 · see citing works
Takano, S., Kubota, T., Nishibori, H., Hasegawa, H., Ishii, Y., Nitori, N., Ochiai, H., Okabayashi, K., Kitagawa, Y., Watanabe, M., et al. (2008) · PubMed · Cited by 47 · see citing works
Li, M., Yuan, H., Ma, L. T., Kong, A. W. Y., Hsin, M. K. Y., Yip, J. H. Y., Underwood, M. J., & Chen, G. G. (2010) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2009-0349oc · Cited by 47 · see citing works
PPAR-γ ligand promotes the growth of APC-mutated HT-29 human colon cancer cells in vitro and in vivo
Choi, I.-H., Kim, Y. H., Kim, J. S., & Seo, J. H. (2007) · Investigational New Drugs · doi:10.1007/s10637-007-9108-x · Cited by 40 · see citing works
Inverse association of PPARγ agonists use and high grade glioma development
Grommes, C., Conway, D. S., Alshekhlee, A., & Barnholtz‐Sloan, J. S. (2010) · Journal of Neuro-Oncology · doi:10.1007/s11060-010-0185-x · Cited by 36 · see citing works
Bartling, B., Hofmann, H.-S., Sohst, A., Hatzky, Y., Somoza, V., Silber, R., & Simm, A. (2011) · Molecular Medicine · doi:10.2119/molmed.2011.00085 · Cited by 33 · see citing works
Wang, G., Han, D. G., Zhang, Y., Xie, X., Wu, Y., Li, S., & Li, M. (2013) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2072-1439.2013.08.69 · Cited by 28 · see citing works
Choi, J., Lee, M. K., Oh, K. H., Kim, Y. S., Choi, H. Y., Baek, S., Jung, K., Woo, J., Lee, S. H., & Kwon, S. Y. (2011) · Tumori Journal · doi:10.1177/030089161109700211 · Cited by 27 · see citing works
Pioglitazone Prevents Smoking Carcinogen-Induced Lung Tumor Development in Mice
Li, M. Y., Kong, A. W. Y., Yuan, H., T., L., Hsin, M. K. Y., Wan, I. Y. P., Underwood, M. J., & Chen, G. G. (2012) · Current Cancer Drug Targets · doi:10.2174/156800912801784848 · Cited by 23 · see citing works
DiNorcia, J., Moroziewicz, D. N., Ippagunta, N., Lee, M. K., Foster, M., Rotterdam, H. Z., Bao, F., Zhou, Y. S., Yan, S. F., Emond, J. C., et al. (2010) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-010-1347-z · Cited by 21 · see citing works
Ueno, T., Teraoka, N., Takasu, S., Nakano, K., Takahashi, M., Yamamoto, M., Fujii, G., Komiya, M., Yanaka, A., Wakabayashi, K., et al. (2012) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2012.13.8.4067 · Cited by 20 · see citing works
Sterenczak, K. A., Joetzke, A., Willenbrock, S., Eberle, N., Lange, S., Junghanß, C., Nolte, I. J. A., Bullerdiek, J., Simón, D., & Escobar, H. M. (2010) · PubMed · Cited by 17 · see citing works
Sterenczak, K. A., Kleinschmidt, S., Wefstaedt, P., Eberle, N., Hewicker‐Trautwein, M., Bullerdiek, J., Nolte, I. J. A., & Escobar, H. M. (2011) · PubMed · Cited by 15 · see citing works
Al‐Taie, O., Graf, T., Illert, B., Katzenberger, T., Mörk, H., Kraus, M. R., Barthelmes, H. U., Scheurlen, M., & Seufert, J. (2009) · Journal of Gastroenterology · doi:10.1007/s00535-009-0086-y · Cited by 13 · see citing works
Kim, S. (2009) · International Journal of Oncology · doi:10.3892/ijo_00000493 · Cited by 12 · see citing works
[The role of peroxisome proliferator-activated receptors (PPAR) in carcinogenesis].
Knapp, P., Jarząbek, K., Błachnio-Zabielska, A. U., & Zbroch, T. (2006) · PubMed · Cited by 9 · see citing works
Activation of PPARγ in myeloid cells promotes lung cancer progression and metastasis
Nemenoff, R. A. (2012) · OncoImmunology · doi:10.4161/onci.19309 · Cited by 8 · see citing works
Jin, H. J., Kim, J., Hong, S. M., Hong, S. J., Park, J. H., Kim, E., Wang, H.-J., Choi, Y. J., Do, I., Joh, J., et al. (2011) · Annals of Surgical Oncology · doi:10.1245/s10434-011-1856-3 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rungratanawanich, W., Qu, Y., Wang, X., Essa, M. M., & Song, B.-J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00561-7 · Cited by 411 · see citing works
PPAR-α Modulators as Current and Potential Cancer Treatments
Chi, T., Wang, M., Wang, X., Ke, Y., Xie, F., Zehuan, L., & Wei, P. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.599995 · Cited by 244 · see citing works
Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention
Lange, N. F., Radu, P., & Dufour, J. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.07.025 · Cited by 137 · see citing works
Danger signals in liver injury and restoration of homeostasis
Han, H., Desert, R., Das, S., Song, Z., Athavale, D., Ge, X., & Nieto, N. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.04.033 · Cited by 127 · see citing works
MASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges
Phoolchund, A. G. S., & Khakoo, S. (2024) · Cancers · doi:10.3390/cancers16020259 · Cited by 127 · see citing works
Yousefnia, S., Momenzadeh, S., Forootan, F. S., Ghaedi, K., & Nasr‐Esfahani, M. H. (2018) · Gene · doi:10.1016/j.gene.2018.01.018 · Cited by 123 · see citing works
Yang, X., Deng, B., Zhao, W., Guo, Y., Wan, Y., Wu, Z., Su, S., Gu, J., Hu, X., Feng, W., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.09.029 · Cited by 111 · see citing works
Self-citationCurrent and emerging strategies for the prevention of hepatocellular carcinoma
Yeo, Y. H., Abdelmalek, M. F., Khan, S. A., Moylan, C. A., Rodriquez, L. M., Villanueva, A., & Yang, J. D. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-01021-z · Cited by 99 · see citing works
Wang, X., Xiang, L., Li, H., Chen, P., Feng, Y., Zhang, J., Yang, N., Li, F., Wang, Y., Zhang, Q., et al. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160922527 · Cited by 76 · see citing works
Hispidulin: A promising flavonoid with diverse anti-cancer properties
Liu, K., Zhao, F., Yan, J., Xia, Z., Jiang, D., & Ma, P. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118395 · Cited by 76 · see citing works
RAGE Suppresses ABCG1-Mediated Macrophage Cholesterol Efflux in Diabetes
Daffu, G. K., Shen, X., Senatus, L. M., Thiagarajan, D., Abedini, A., del Pozo, C. H., Rosario, R., Song, F., Friedman, R. A., Ramasamy, R., et al. (2015) · Diabetes · doi:10.2337/db15-0575 · Cited by 75 · see citing works
Muthyalaiah, Y. S., Jonnalagadda, B., John, C. M., & Arockiasamy, S. (2021) · Glycoconjugate Journal · doi:10.1007/s10719-021-10031-x · Cited by 72 · see citing works
Qiao, Y., Zhang, X. L., Zhang, Y., Wang, Y., Xu, Y., Liu, X., Sun, F., & Wang, J. (2016) · Diabetes · doi:10.2337/db15-1057 · Cited by 64 · see citing works
Self-citationHollenbach, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112466 · Cited by 62 · see citing works
Ma, Y., Wang, J.-G., Xiao, W., & Fan, X.-M. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1410668 · Cited by 63 · see citing works
Vella, V., Lappano, R., Bonavita, E., Maggiolini, M., Clarke, R. B., Belfiore, A., & Francesco, E. M. D. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad005 · Cited by 56 · see citing works
The Role of PPARs in Breast Cancer
Zhao, B., Xin, Z., Ren, P., & Wu, H. (2022) · Cells · doi:10.3390/cells12010130 · Cited by 50 · see citing works
Sun, J., Yu, L., Qu, X., & Huang, T. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1184794 · Cited by 52 · see citing works
MAFLD: an optimal framework for understanding liver cancer phenotypes
Crane, H., Gofton, C., Sharma, A., & George, J. (2023) · Journal of Gastroenterology · doi:10.1007/s00535-023-02021-7 · Cited by 45 · see citing works
Ha, X., Wang, J., Chen, K., Deng, Y., Zhang, X., Feng, J., Li, X., Zhu, J., Ma, Y., Qiu, T., et al. (2020) · Cancer Management and Research · doi:10.2147/cmar.s236301 · Cited by 44 · see citing works
RetractedRepurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp
Hijazi, M. A., Gessner, A., & El‐Najjar, N. (2023) · Cancers · doi:10.3390/cancers15123199 · Cited by 42 · see citing works
Pioglitazone Reduces Hepatocellular Carcinoma Development in Two Rodent Models of Cirrhosis
Li, S., Ghoshal, S., Sojoodi, M., Arora, G., Masia, R., Erstad, D. J., Lanuti, M. D., Hoshida, Y., Baumert, T. F., Tanabe, K. K., et al. (2018) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-018-4004-6 · Cited by 41 · see citing works
Guo, M., Guo, G., Xiao, J., Sheng, X., Zhang, X., Tie, Y., Cheng, Y., & Ji, X. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13601 · Cited by 39 · see citing works
Katoch, S., Sharma, V., & Patial, V. (2022) · World Journal of Gastroenterology · doi:10.3748/wjg.v28.i28.3535 · Cited by 34 · see citing works
Advanced glycation end products and their adverse effects: The role of autophagy
Sruthi, C. R., & Raghu, K. G. (2021) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22710 · Cited by 33 · see citing works
Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases
Chung, W., Promrat, K., & Wands, J. R. (2020) · World Journal of Hepatology · doi:10.4254/wjh.v12.i9.533 · Cited by 33 · see citing works
Takino, J.-I. (2015) · World Journal of Hepatology · doi:10.4254/wjh.v7.i23.2459 · Cited by 32 · see citing works
Inhibition of RAGE Axis Signaling: A Pharmacological Challenge
Armando Rojas, R., Morales, M. A., González, I., & Araya, P. (2018) · Current Drug Targets · doi:10.2174/1389450119666180820105956 · Cited by 31 · see citing works
Wu, J., Lu, W., & Cui, L. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2015.4460 · Cited by 29 · see citing works
Prostanoid EP4 agonist L-902,688 activates PPARγ and attenuates pulmonary arterial hypertension
Li, H.-H., Hsu, H., Chang, G., Chen, I.-C., Ho, W., Hsu, P.-C., Chen, W.-J., Pang, J. S., Huang, C.-C., & Lai, Y. (2017) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00245.2017 · Cited by 29 · see citing works
PPAR Ligands Function as Suppressors That Target Biological Actions of HMGB1
Ying, S., Xiao, X., Chen, T., & Lou, J. (2016) · PPAR Research · doi:10.1155/2016/2612743 · Cited by 28 · see citing works
Wu, J., Cui, L., Yuan, J., Wang, Y., & Shu, S. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6224 · Cited by 27 · see citing works
Pan, Y., Li, Y., Fan, H., Cui, H., Chen, Z., Wang, Y., Jiang, M., & Wang, G. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117089 · Cited by 25 · see citing works
Unexploited Antineoplastic Effects of Commercially Available Anti-Diabetic Drugs
Papanagnou, P., Stivarou, T., & Tsironi, M. (2016) · Pharmaceuticals · doi:10.3390/ph9020024 · Cited by 25 · see citing works
Hsu, H.-T., Sung, M., Lee, C.-C., Kuo, Y., Chi, C., Lee, H., & Hsia, C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081226 · Cited by 23 · see citing works
Gao, H., Li, H., Li, W., Shen, X., & Di, B. (2017) · Medical Science Monitor · doi:10.12659/msm.907401 · Cited by 19 · see citing works
A Sterol from Soft Coral Induces Apoptosis and Autophagy in MCF-7 Breast Cancer Cells
Weng, J., Chiu, C., Hu, J.-L., Feng, C., Huang, C., Bai, L., & Sheu, J. (2018) · Marine Drugs · doi:10.3390/md16070238 · Cited by 18 · see citing works
Wang, L., Min, Z., Wang, X., Hu, M., Song, D., Ren, Z., Cheng, Y., & Wang, Y. (2018) · Oncology Letters · doi:10.3892/ol.2018.8981 · Cited by 17 · see citing works
Wang, Q., Liang, N. N., Liu, C., Li, J., Bai, Y., Lei, S., Huang, Q., Sun, L., Tang, L., Zeng, C., et al. (2023) · British Journal of Cancer · doi:10.1038/s41416-023-02418-4 · Cited by 15 · see citing works
Pioglitazone inhibits EGFR/MDM2 signaling-mediated PPARγ degradation.
Shi, J.-J., Zhang, W.-B., You, M., Xu, Y., Hou, Y.-Z., & Jin, J.-H. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.09.010 · Cited by 14 · see citing works
Self-citationHan, W., Wang, N., Kong, R., Bao, W., & Lu, J. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03288-9 · Cited by 15 · see citing works
Identification of a Triterpenoid as a Novel PPARγ Activator Derived from Formosan Plants
Weng, J., Bai, L., & Lin, W. (2017) · Phytotherapy Research · doi:10.1002/ptr.5900 · Cited by 15 · see citing works
Therapeutic Potential and Challenges of Pioglitazone in Cancer Treatment
Vasileiou, M., Diamantoudis, S. C., Tsianava, C., & Nguyen, N. P. (2025) · Applied Sciences · doi:10.3390/app15041925 · Cited by 13 · see citing works
The Role of Type 2 Diabetes Mellitus–Related Risk Factors and Drugs in Hepatocellular Carcinoma
Mai, Y., Meng, L.-H., Deng, G.-L., & Qin, Y.-F. (2024) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s441672 · Cited by 11 · see citing works
Emerging Roles of High-mobility Group Box-1 in Liver Disease
Wang, L., Dong, Z., Zhang, Y., & Peng, L. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2024.00317 · Cited by 8 · see citing works
Jang, J., Lee, T. J., Sung, E., Song, I., & Kim, J. (2021) · Oncology Letters · doi:10.3892/ol.2021.13004 · Cited by 7 · see citing works
Immunometabolic factors contributing to obesity-linked hepatocellular carcinoma
Akl, M. G., & Widenmaier, S. B. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1089124 · Cited by 6 · see citing works
Yang, X., Xiao, X., Wang, H., Li, Y., Wang, L., Li, G., & Deng, S. (2018) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2018/3450141 · Cited by 5 · see citing works
Wen, J., Geng, L., Wang, R., Zhang, X., Sui, Y., Liu, X., & Han, X. (2025) · Journal of Molecular Histology · doi:10.1007/s10735-025-10446-y · Cited by 4 · see citing works
Self-citationChiang, C., Chang, Y., Wang, S., Chen, Y., See, X. Y., Peng, C., Hsia, Y. P., Chiang, C., Chiang, C., & Peng, C. (2023) · Cancer Medicine · doi:10.1002/cam4.5734 · Cited by 4 · see citing works
Armando Rojas, R., Lindner, C., Schneider, I., González, I., & Morales, M. A. (2022) · World Journal of Gastroenterology · doi:10.3748/wjg.v28.i39.5679 · Cited by 3 · see citing works
Xie, R., Luo, Y., Bao, B., Wu, X., Guo, J., Wang, J., Qu, X., Che, X., & Zheng, C. (2024) · Drug Development Research · doi:10.1002/ddr.70014 · Cited by 2 · see citing works
Letter: metformin treatment and hepatocellular carcinoma risk in non‐alcoholic fatty liver disease
Doğru, T., Kırık, A., & Sönmez, A. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15462 · Cited by 2 · see citing works
Pioglitazone-Based Combination Approaches for Non-Small-Cell Lung Cancer
Aluru, S., Thyagarajan‐Sahu, A., & Sahu, R. P. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17111416 · Cited by 1 · see citing works
Nelappana, M. B., Wityk, P., Applegate, C. C., Okoro, G., Kalinowski, L., Dobrucki, I. T., & Dobrucki, L. W. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.13.705839 · Cited by 1 · see citing works
- Authors
- Yang, Y., Zhao, L., Huang, B., Wang, R., Yuan, S., Tao, Q., Xu, Y., Sun, H., Lin, C., & Zhou, W.
- Affiliations
- Second Military Medical University (CN)
- Suzhou Municipal Hospital (CN)
- Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai China
- Shanghai Dingdian Biotechnology Limited Company Shanghai China
- Corresponding author
- Lin, Chuan
- Venue
- Molecular Carcinogenesis
- Publisher
- Wiley
- Published
- 2014-10-12
- Volume
- 54
- Issue
- 12
- Pages
- 1584-1595
- ISSN
- 0899-1987 (ISSN-L)
- 1098-2744
- OpenAlex
- W2116561826
- Cited by
- 55
- References
- 42
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 1 · 2018: 8 · 2017: 5 · 2016: 5 · 2015: 3 · 2012: 1
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81201940, 81221061, 81101512)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- pioglitazone, PPARγ agonists, hepatocellular carcinoma, RAGE, advanced glycation end products, tumor invasion, cell proliferation, apoptosis, cell cycle arrest, NF-κB, HMGB1, p38 MAPK, MMP-2, cyclin D1, pathological staging, lymph-vascular space invasion
- MeSH terms
- Receptor for Advanced Glycation End Products, Pioglitazone, Cell Cycle, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Neoplasm Invasiveness, Signal Transduction, Apoptosis, Thiazolidinediones, Cell Line, Tumor, PPAR gamma, Cell Proliferation, Hep G2 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
