Clinical and Translational Oncology

, Volume 21, Issue 4, pp 404–411 | Cite as

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

  • H. Guo
  • Z. Xiang
  • Y. Zhang
  • D. SunEmail author
Research Article



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.


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.


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.


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 cancer.


6PGD Cervical cancer Physcion AMPK RhoA Rac1 



This work was supported by a research grant provided by Hubei Provincial Science and Technology Commission (Grant no. EK100826).

Compliance of ethical standards

Conflicts of interest

All authors declare no conflicts of interests.

Research involving human participants and/or animals

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12094_2018_1937_MOESM1_ESM.doc (251 kb)
Supplementary material 1 (DOC 251 kb)


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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyXiangyang No. 1 People’s Hospital, Hubei University of MedicineXiangyangChina
  2. 2.Department of PathologyXiangyang No. 1 People’s Hospital, Hubei University of MedicineXiangyangChina
  3. 3.Department of PharmacyXiangyang Maternity and Child Health Care HospitalXiangyangChina
  4. 4.Department of Obstetrics and GynecologyHanchuan People’s HospitalHanchuan, XiaoganChina

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