Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail‑glycolysis pathways

Jia,Luoqi; Zhou,Jiayi; Zhao,Hongbo; Jin,Hongyan; Lv,Minzhi; Zhao,Naiqing; Zheng,Zhizhong; Lu,Yiling; Ming,Yanlin; Yu,Yinhua

doi:10.3892/or.2017.5886

Corilagin sensitizes epithelial ovarian cancer to chemotherapy by inhibiting Snail‑glycolysis pathways

Authors:
- Luoqi Jia
- Jiayi Zhou
- Hongbo Zhao
- Hongyan Jin
- Minzhi Lv
- Naiqing Zhao
- Zhizhong Zheng
- Yiling Lu
- Yanlin Ming
- Yinhua Yu
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Affiliations: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai 200090, P.R. China, Deparment of Biostatistics, School of Public Health, Fudan University, Shanghai 200011, P.R. China, Key Laboratory of Xiamen City for Plant Introduction and Quarantine and Plant Products, Xiamen Overseas Chinese Subtropical Plant Introduction Garden, Xiamen, Fujian 361002, P.R. China, Department of Systems Biology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA
Published online on: August 7, 2017 https://doi.org/10.3892/or.2017.5886
Pages: 2464-2470

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Abstract

We identified that corilagin is a major component extracted from a well-known hepatoprotective and antiviral medicinal herb, Phyllanthus niruri L with antitumor activity. Our previous study found that corilagin inhibited the growth of ovarian cancer cells via the TGF-β/AKT/ERK signaling pathways. Recently, we demonstrated that corilagin enhanced the sensitivity of ovarian cancer cells to chemotherapy. Ovarian cancer cell lines, SKOv3ip, Hey and HO-8910PM-Snail, were treated with different concentrations of corilagin in combination with paclitaxel and carboplatin. Corilagin distinctly enhanced the inhibitory effects of paclitaxel and carboplatin. To understand the mechanisms involved in the chemo-sensitization by corilagin, we performed reverse phase protein array analysis to determine the signaling networks induced by corilagin. We observed that both paclitaxel and carboplatin upregulated the expression levels of several apoptotic and death-related proteins, such as caspase 3, caspase 7 and PDCD4, which were further enhanced when combined with corilagin. Meanwhile, corilagin induced distinct pathways to paclitaxel and carboplatin treatment. We also performed isobaric tags for relative and absolute quantitation proteomics analysis in corilagen-treated ovarian cancer cells. This analysis indicated that corilagin is mainly involved in the glycolysis pathway. Seahorse XF96 extracellular acidification rate analysis confirmed that corilagin inhibited glycolysis by downregulation of CD44 and STAT3. In summary, our observations indicate that corilagin sensitized epithelial ovarian cancer cells to paclitaxel and carboplatin treatment by primarily inhibiting Snail-glycolysis pathways. Corilagin is a herbal medicine with low toxic effects to normal cells, particularly hepatoprotective, and may be an ideal complimentary medicine when combined with highly toxic chemotherapeutic agents.

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