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Cited by 34Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerBiochemical and Molecular Research

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Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in cervical cancer via AMPK-independent inhibition of RhoA and Rac1

Guo, H., Xiang, Z., Zhang, Y., Sun, D.·2019·Clinical and Translational Oncology
DOI 10.1007/s12094-018-1937-x
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Abstract

Background The oxidative pentose phosphate pathway (PPP) is essential for cancer metabolism and growth. However, the contribution of 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of PPP, to cervical cancer development remains largely unknown. Methods mRNA and protein levels of 6PGD were analyzed in cervical cancer cells and tissues derived from patients and compared to normal counterparts. Using cell culture system and xenograft mouse model, the functions of 6PGD in cervical cancer are determined and its molecular mechanism is analyzed. 6PGD inhibitor physcion and siRNA knockdown were used. Results In this work, we demonstrate that 6PGD is aberrantly upregulated and activated in cervical cancer cells and patient tissues compared to normal counterparts. Using different approaches and preclinical models, we show that 6PGD inhibition decreases growth and migration, and enhances chemosensitivity in cervical cancer. Mechanistically, inhibition of 6PGD activates AMP-activated protein kinase (AMPK) and decreases RhoA and Rac1 activities. AMPK depletion significantly reduces the effects of 6PGD inhibition in decreasing RhoA and Rac1 activities, growth and migration in cervical cancer cells. Conclusions Our work is the first to demonstrate the aberrant expression of 6PGD and its predominant roles in cervical cancer cell growth and migration, via a AMPK-dependent activation. Our findings suggest 6PGD as a potential therapeutic target to enhance chemosensitivity in cervical canc…

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Metadata

Authors
Guo, H., Xiang, Z., Zhang, Y., & Sun, D.
Affiliations
Hubei University of Medicine (CN)
Corresponding author
Sun, D.
ORCID
Venue
Clinical and Translational Oncology
Publisher
Springer Science and Business Media LLC
Published
2018-09-04
Volume
21
Issue
4
Pages
404-411
ISSN
  • 1699-048X (ISSN-L)
  • 1699-3055
DOI
10.1007/s12094-018-1937-x
OpenAlex
W2892211035
Cited by
34
References
0
Citations by year
2025: 3 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 10 · 2019: 4
FWCI
1.51
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Clinical & Translational Oncology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Hubei Provincial Science and Technology Commission (EK100826)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
6-phosphogluconate dehydrogenase, cervical cancer, oxidative pentose phosphate pathway, AMPK, RhoA, Rac1, chemosensitivity, cell migration, cell growth, physcion, therapeutic target
MeSH terms
Animals, Cell Movement, Uterine Cervical Neoplasms, Emodin, Female, Humans, Phosphogluconate Dehydrogenase, Tumor Cells, Cultured, Biomarkers, Tumor, Gene Expression, Mice, SCID, Chemotherapy, Adjuvant, Apoptosis, Paclitaxel, rhoA GTP-Binding Protein, rac1 GTP-Binding Protein, Xenograft Model Antitumor Assays, Cell Proliferation, AMP-Activated Protein Kinases

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CoChat. (2026). Citation check: Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in cervical cancer via AMPK-independent inhibition of RhoA and Rac1. https://app.cochat.ai/papers/10.1007/s12094-018-1937-x
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Guo, H., Xiang, Z., Zhang, Y., & Sun, D. (2019). Inhibiting 6-phosphogluconate dehydrogenase enhances chemotherapy efficacy in cervical cancer via AMPK-independent inhibition of RhoA and Rac1. Clinical and Translational Oncology. https://doi.org/10.1007/s12094-018-1937-x