Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer

Kuo Chang Wen, Pi Lin Sung, Alexander T.H. Wu, Ping Chieh Chou, Jun Hung Lin, Chi Ying F. Huang, Sai Ching J. Yeung, Mong Hong Lee

研究成果: 雜誌貢獻文章同行評審

摘要

Background: Ovarian cancer is the leading cause of cancer-related death among women. Complete cytoreductive surgery followed by platinum-taxene chemotherapy has been the gold standard for a long time. Various compounds have been assessed in an attempt to combine them with conventional chemotherapy to improve survival rates or even overcome chemoresistance. Many studies have shown that an antidiabetic drug, metformin, has cytotoxic activity in different cancer models. However, the synergism of metformin as a neoadjuvant formula plus chemotherapy in clinical trials and basic studies remains unclear for ovarian cancer. Methods: We applied two clinical databases to survey metformin use and ovarian cancer survival rate. The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy. Results: We found that ovarian cancer patients treated with metformin had significantly longer overall survival than patients treated without metformin. The protein profile induced by low-concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway. In combination with chemotherapy, the neoadjuvant metformin protocol showed beneficial synergistic effects in vitro and in vivo. Conclusions: This study shows that neoadjuvant metformin at clinically relevant dosages is efficacious in treating ovarian cancer, and the results can be used to guide clinical trials.

原文英語
文章編號95
期刊Journal of Ovarian Research
13
發行號1
DOIs
出版狀態已發佈 - 八月 21 2020

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynaecology

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