Knockdown of PLC-gamma-2 and calmodulin 1 genes sensitizes human cervical adenocarcinoma cells to doxorubicin and paclitaxel
Open accessAbstract
Background: RNA interference (RNAi) is a powerful approach in functional genomics to selectively silence messenger mRNA (mRNA) expression and can be employed to rapidly develop potential novel drugs against a complex disease like cancer. However, naked siRNA being anionic is unable to cross the anionic cell membrane through passive diffusion and therefore, delivery of siRNA remains a major hurdle to overcome before the potential of siRNA technology can fully be exploited in cancer. pH-sensitive carbonate apatite has recently been developed as an efficient tool to deliver siRNA into the mammalian cells by virtue of its high affinity interaction with the siRNA and the desirable size distribution of the resulting siRNA-apatite complex for effective cellular endocytosis. Moreover, internalized siRNA was found to escape from the endosomes in a time-dependent manner and efficiently silence gene expression. Results: Here we show that carbonate apatite-mediated delivery of siRNA against PLC-gamma-2 (PLCG2) and calmodulin 1 (CALM1) genes has led to the sensitization of a human cervical cancer cell line to doxorubicin- and paclitaxel depending on the dosage of the individual drug whereas no such enhancement in cell death was observed with cisplatin irrespective of the dosage following intracellular delivery of the siRNAs. Conclusion: Thus, PLCG2 and CALM1 genes are two potential targets for gene knockdown in doxorubicin and paclitaxel-based chemotherapy of cervical cancer.
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In human cervical adenocarcinoma cells, in vitro siRNA knockdown of PLCγ2 and calmodulin 1 led to increased sensitivity to doxorubicin and paclitaxel, but not Cisplatin.
“PLCγ2 was also implicated in cervical adenocarcinoma, where in vitro siRNA knockdown of PLCγ2, and calmodulin 1, in human cervical adenocarcinoma cells led to an increased sensitivity to doxorubicin and paclitaxel, but not Cisplatin (147).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [147]
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Cites
Clapham, D. E. (2007) · Cell · doi:10.1016/j.cell.2007.11.028 · Cited by 4,175 · see citing works
Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer
Roberts, P. J., & Der, C. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210422 · Cited by 2,788 · see citing works
Regulation of Cell Cycle Progression by Calcium/Calmodulin-Dependent Pathways
Kahl, C. R., & Means, A. R. (2003) · Endocrine Reviews · doi:10.1210/er.2003-0008 · Cited by 493 · see citing works
Houghton, A. N., & Polsky, D. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00161-7 · Cited by 415 · see citing works
Activation of programmed cell death by anticancer agents: cisplatin as a model system.
Eastman, A. R. (1990) · PubMed · Cited by 398 · see citing works
Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study
Cherrier, M., Borghesani, P., Shelton, A., & Higano, C. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-1 · Cited by 337 · see citing works
siRNA therapeutics: big potential from small RNAs
Ryther, R. C. C., Flynt, A. S., Phillips, J. A., & Patton, J. G. (2004) · Gene Therapy · doi:10.1038/sj.gt.3302356 · Cited by 301 · see citing works
Drug delivery of siRNA therapeutics: potentials and limits of nanosystems
Reischl, D., & Zimmer, A. (2008) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2008.06.001 · Cited by 253 · see citing works
Nonviral methods for siRNA delivery
Gao, K., & Huang, L. (2009) · Molecular Pharmaceutics · doi:10.1021/mp800134q · Cited by 244 · see citing works
Delivery Vehicles for Small Interfering RNA In Vivo
de Fougerolles, A. R. (2008) · Human Gene Therapy · doi:10.1089/hum.2008.928 · Cited by 228 · see citing works
van de Water, F. M., Boerman, O. C., Wouterse, A. C., Peters, J. G. P., Rüssel, F. G. M., & Masereeuw, R. (2006) · Drug Metabolism and Disposition · doi:10.1124/dmd.106.009555 · Cited by 217 · see citing works
Phosphoinositide 3-Kinase Signalling Pathways in Tumor Progression, Invasion and Angiogenesis
Brader, S., & Eccles, S. A. (2004) · Tumori Journal · doi:10.1177/030089160409000102 · Cited by 216 · see citing works
In Vivo Application of RNA Interference: From Functional Genomics to Therapeutics
Lu, P. Y., Xie, F. Y., & Woodle, M. C. (2005) · Advances in genetics · doi:10.1016/s0065-2660(05)54006-9 · Cited by 180 · see citing works
Chemosensitization of cancer cells by siRNA using targeted nanogel delivery
Dickerson, E. B., Blackburn, W. H., Smith, M. H., Kapa, L. B., Lyon, L. A., & McDonald, J. F. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-10 · Cited by 140 · see citing works
Gradin, H. M., Marklund, U., Larsson, N., Chatila, T. A., & Gullberg, M. H. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3459 · Cited by 134 · see citing works
Physiological Roles Of The Ca2+/Cam-Dependent Protein kinase Cascade In Health and Disease
COLOMER, J., & Means, A. R. (2007) · Springer eBooks · doi:10.1007/978-1-4020-6191-2_7 · Cited by 122 · see citing works
Chemotherapy for recurrent cervical cancer
Pectasides, D. G., Kamposioras, K. V., Papaxoinis, G., & Pectasides, E. (2008) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2008.05.006 · Cited by 113 · see citing works
Li, C., Heim, R., Lü, P., Pu, Y., Tsien, R. Y., & Chang, D. C. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.10.1567 · Cited by 102 · see citing works
Jang, M. K., Goo, Y. H., Sohn, Y. C., Kim, Y. S., Lee, S., Kang, H., Cheong, J., & Lee, J. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010211200 · Cited by 83 · see citing works
Cisplatin in advanced cancer of the cervix: an update.
Alberts, D. S., Garcia, D. J., & Mason-Liddil, N. (1991) · PubMed · Cited by 81 · see citing works
RNA Interference as A Gene-Specific Approach for Molecular Medicine
Grünweller, A., & Hartmann, R. K. (2005) · Current Medicinal Chemistry · doi:10.2174/092986705774933489 · Cited by 76 · see citing works
Hossain, S., Stanislaus, A., Chua, M. J., Tada, S., Tagawa, Y., Chowdhury, E. H., & Akaike, T. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.06.024 · Cited by 75 · see citing works
Self-citationControl of HIV-1 replication by RNA interference
Lee, N. S., & Rossi, J. J. (2004) · Virus Research · doi:10.1016/j.virusres.2004.01.015 · Cited by 75 · see citing works
Mitochondrial diacylglycerol initiates protein-kinase-D1-mediated ROS signaling
Cowell, C. F., Döppler, H. R., Yan, I. K., Haußer, A., Umezawa, Y., & Störz, P. (2009) · Journal of Cell Science · doi:10.1242/jcs.041061 · Cited by 67 · see citing works
Microtubule-Stabilizing Natural Products as Promising Cancer Therapeutics
Gallagher, B., Jr. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707782794014 · Cited by 45 · see citing works
Management of cervical cancer in pregnancy.
Method, M., & Brost, B. (1999) · Seminars in surgical oncology · doi:10.1002/(sici)1098-2388(199904/05)16:3 · Cited by 44 · see citing works
Nuclear targeting of viral and non-viral DNA
Chowdhury, E. H. (2009) · Expert Opinion on Drug Delivery · doi:10.1517/17425240903025744 · Cited by 36 · see citing works
Self-citationGenome‐wide application of RNAi to the discovery of potential drug targets
Ito, M., Kawano, K., Miyagishi, M., & Taira, K. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.08.015 · Cited by 32 · see citing works
Kim, M., Jung, J., & Lee, K. (2009) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2009.02.002 · Cited by 29 · see citing works
Strategies for tumor-directed delivery of siRNA
Chowdhury, E. H. (2011) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2011.554817 · Cited by 21 · see citing works
Self-citationNishio, K., Sugimoto, Y., Fujiwara, Y., Ohmori, T., MORIKAGE, T., Takeda, Y., Ohata, M., & Saijo, N. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115758 · Cited by 20 · see citing works
Treatment of cervical cancer in Italy: Strategies and their impact on the women
Vincenzo, R. D., Amadio, G., Ricci, C., Licameli, A., Ferrandina, G., Capelli, G., & Scambia, G. (2009) · Vaccine · doi:10.1016/j.vaccine.2008.11.110 · Cited by 17 · see citing works
Stanislaus, A., Hossain, S., Chua, M. J., Kunnath, A. P., Wen, Q. C., Syakira, S. N., Siong, G. Y., Loong, S. W., Othman, I., Akaike, T., et al. (2011) · Drugs and Therapy Studies · doi:10.4081/dts.2011.e8 · Cited by 8 · see citing works
Self-citationEndometrial cancer: The management of high-risk disease
Kristensen, G. B., & Trope, C. G. (2004) · Current Oncology Reports · doi:10.1007/s11912-004-0078-2 · Cited by 8 · see citing works
Thompson, M. G., & Hickman, J. A. (1991) · European Journal of Cancer and Clinical Oncology · doi:10.1016/0277-5379(91)90094-t · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The many faces of calmodulin in cell proliferation, programmed cell death, autophagy, and cancer
Berchtold, M. W., & Villalobo, A. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.10.021 · Cited by 312 · see citing works
The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration
Jackson, J. T., Mulazzani, E., Nutt, S. L., & Masters, S. L. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100905 · Cited by 113 · see citing works
Differentially expressed genes and gene networks involved in pig ovarian follicular atresia
Terenina, E. E., Fabre, S., Bonnet, A., Monniaux, D., Robert-Granié, C., SanCristobal, M., Sarry, J., Vignoles, F., Gondret, F., Monget, P., et al. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00069.2016 · Cited by 69 · see citing works
Singh, P. K., Sharma, S., & Rath, S. K. (2021) · Phytomedicine Plus · doi:10.1016/j.phyplu.2021.100148 · Cited by 25 · see citing works
Kang, J. U. (2013) · Molecular Medicine Reports · doi:10.3892/mmr.2013.1686 · Cited by 23 · see citing works
Schomberg, J. (2019) · Cancer Informatics · doi:10.1177/1176935119889911 · Cited by 17 · see citing works
Tiash, S., & Chowdhury, E. H. (2018) · Journal of drug targeting · doi:10.1080/1061186x.2018.1525388 · Cited by 17 · see citing works
Self-citationLange, C., Weber, A. M., Schmidt, R., Schroeder, C., Strowitzki, T., & Germeyer, A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248103 · Cited by 16 · see citing works
Kunnath, A. P. (2014) · Journal of Cancer Science & Therapy · doi:10.4172/1948-5956.1000256 · Cited by 16 · see citing works
Loss of 9p21 Regulatory Hub Promotes Kidney Cancer Progression by Upregulating HOXB13
Baietti, M. F., Zhao, P., Crowther, J., Sewduth, R. N., Troyer, L. D., Dêbiec‐Rychter, M., & Sablina, A. A. (2021) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-20-0705 · Cited by 13 · see citing works
Liu, C. W., & Lin, L. (2013) · Journal of Nanoparticle Research · doi:10.1007/s11051-013-1956-z · Cited by 13 · see citing works
Ajorloo, F., Vaezi, M., Saadat, A., Safaee, S. R., Gharib, B., Ghanei, M., Siadat, S. D., Vaziri, F., Fateh, A., Pazhouhandeh, M., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183969 · Cited by 13 · see citing works
Jiang, R., Teng, Y., Huang, Y., Gu, J., Ma, L., Li, M., & Zhou, Y. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2014.59 · Cited by 11 · see citing works
Knockdown of ROS1 gene sensitizes breast tumor growth to doxorubicin in a syngeneic mouse model
Tiash, S., Chua, M. J., & Chowdhury, E. H. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3452 · Cited by 11 · see citing works
Self-citationKunnath, A. P. (2015) · Journal of Nanomedicine & Nanotechnology · doi:10.4172/2157-7439.1000278 · Cited by 8 · see citing works
PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications
Jiang, P., Wang, M., Zhang, C., Li, X., Wang, Z. Q., Guo, Y., Zhang, J., Yan, W., & Xi, X. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-025-07632-7 · Cited by 6 · see citing works
Stanislaus, A., Kunnath, A. P., Tiash, S., Fatemian, T., Kamaruzman, N. I., Bakhtiar, A., Mustak, S., Hossain, S., Akaike, T., & Chowdhury, E. H. (2013) · Drugs and Therapy Studies · doi:10.4081/dts.2013.e7 · Cited by 5 · see citing works
Self-citationIdentifying differential expression of human genes under physical, chemical and biotic stresses
Saba Afzal, M. Y. K. B. (2021) · International Journal of Biosciences (IJB) · doi:10.12692/ijb/18.6.42-50
Identification of potential drug targets associated with cervicitis based on Mendelian randomization
Liang, W., Bai, Y., Huang, X., Zhang, H., Huang, X., Liang, J., Huang, J., & Huang, B. (2026) · Network Modeling Analysis in Health Informatics and Bioinformatics · doi:10.1007/s13721-026-00766-8
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Šmijáková, E., Brim, L., Pastva, S., & Šafránek, D. (2026) · Bioinformatics · doi:10.1093/bioinformatics/btag275
- Authors
- Stanislaus, A., Bakhtiar, A., Salleh, D., Tiash, S., Fatemian, T., Hossain, S., Akaike, T., & Chowdhury, E. H.
- Affiliations
- Monash University Malaysia (MY)
- IMU University (MY)
- Tokyo Institute of Technology (JP)
- Corresponding author
- Chowdhury, Ezharul Hoque
- Venue
- Cancer Cell International
- Published
- 2012-06-18
- Volume
- 12
- Issue
- 1
- Pages
- 30-30
- ISSN
- 1475-2867 (ISSN-L)
- PMC
- PMC3407783
- OpenAlex
- W2097214456
- Cited by
- 20
- References
- 35
- Citations by year
- 2026: 3 · 2021: 5 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 4
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Cancer Cell International (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Greater South Information System
- Funders
- Kementerian Sains, Teknologi dan Inovasi
- Ministério da Ciência, Tecnologia e Inovação
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- cervical adenocarcinoma, doxorubicin, paclitaxel, cisplatin, chemosensitization, siRNA delivery, carbonated hydroxyapatite, pH-responsive nanoparticles, gene knockdown, RNA interference, drug resistance
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