Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer
- PDF / 3,363,537 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 1 Downloads / 143 Views
RESEARCH
Open Access
Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer Kuo-Chang Wen1,2† , Pi-Lin Sung1,2,3†, Alexander T. H. Wu4, Ping-Chieh Chou5,6, Jun-Hung Lin7, Chi-Ying F. Huang8, Sai-Ching J. Yeung9* and Mong-Hong Lee10*
Abstract 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. Keywords: Neoadjuvant metformin, Ovarian cancer, Clinically relevant dosage, AKT/mTOR pathway, Synergistic effects
* Correspondence: [email protected]; [email protected] † Kuo-Chang Wen and Pi-Lin Sung share first authorship. 9 Department of Emergency Medicine, Division of Internal Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA 10 Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou 510655, P.R. China Full list of author information is available at the end of the article
© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the
Data Loading...
