Metformin combined with cisplatin inhibits the ovarian cancer cell growth and invasion in vitro: an experimental study

• Main Authors: Ni Liu, Dan Pi, Chun-Mei Liu
• Format: Article
• Language: English
• Published: Editorial Board of Journal of Hainan Medical University 2018-01-01
• Series: Journal of Hainan Medical University
• Subjects: Department of Obstetrics and Gynecology; Chongqing Qianjiang National Hospital; Chongqing; 409000. Fund Project: Science and Technology Project of Qianjiang District No: 2016056. 1. Introduction Ovarian cancer is one of the most common malignant tumors in the female reproductive system. Surgical resection and chemotherapy are the main treatments. Because ovarian cancer cells are more sensitive to chemotherapy drugs; especially platinum drugs; the platinum-based intravenous chemotherapy is widely used in the treatment of advanced ovarian cancer[1; some patients with ovarian cancer can develop drug resistance during chemotherapy; which will affect the efficacy of chemotherapy[3]. Metformin is a kind of insulin sensitizer for diabetes treatment; it has been confirmed in recent years that it has anti-tumor effect and chemotherapy drug sensitization effect; and its combination with a variety of chemotherapy drugs can enhance the killing effect of chemotherapy drugs on tumor cells[4]. In the progression of the course of ovarian cancer; the growth and invasion of cancer cells involve the changes in the expression of multiple proliferationrelated genes and invasion-related genes. In the following studies; we specifically analyzed the effects of metformin combined with cisplatin on the expression of genes associated with ovarian cancer cell growth and invasion in vitro. 2. Experimental materials and methods 2.1 Experimental materials Ovarian cancer SKOV3 cell lines were bought in the cell bank of Chinese Academy of Sciences; DMEM; fetal bovine serum and 0.125% trypsin for cell culture were purchased in Hyclone Company; cisplatin and metformin were bought in the Sigma Company; RIPA lysate was purchased in Shanghai Beyotime Company; and enzyme-linked immunosorbent assay kits were purchased from Shanghai Westang Biotechnology Company. Objective: To study the effect of metformin combined with cisplatin on the expression of genes related to ovarian cancer cell growth and invasion in vitro. Methods: SKOV3 ovarian cancer cell lines were cultured and randomly divided into the control group treated with serumfree DMEM; the DDP group treated with serum-free DMEM containing 10 μmol/L cisplatin; the MET group treated with serum-free DMEM containing 10 mmol/L metformin and the DDP+MET group treated with serum-free DMEM containing 10 μmol/L cisplatin and 10 mmol/L metformin. Results: 24 h after treatment; GRP78; TBX2; CyclinD1; Ki-67; Ovarian cancer; Metformin; Cisplatin; Proliferation; Invasion
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Objective: To study the effect of metformin combined with cisplatin on the expression of genes related to ovarian cancer cell growth and invasion in vitro. Methods: SKOV3 ovarian cancer cell lines were cultured and randomly divided into the control group treated with serumfree DMEM, the DDP group treated with serum-free DMEM containing 10 μmol/L cisplatin, the MET group treated with serum-free DMEM containing 10 mmol/L metformin and the DDP+MET group treated with serum-free DMEM containing 10 μmol/L cisplatin and 10 mmol/L metformin. Results: 24 h after treatment, GRP78, TBX2, CyclinD1, Ki-67, MTA1, CTHRC1, Slug and MMP2 protein expression in DDP group, MET group and DDP+MET group were significantly lower than those in control group whereas Fn14, NDRG2, SOCS1, Beclin1 and ST7L protein expression were significantly higher than those of control group; GRP78, TBX2, CyclinD1, Ki-67, MTA1, CTHRC1, Slug and MMP2 protein expression in DDP+MET group were significantly lower than those in DDP group and MET group whereas Fn14, NDRG2, SOCS1, Beclin1 and ST7L protein expression were significantly higher than those in DDP group and MET group. Conclusion: metformin combined with cisplatin can inhibit the expression of pro-proliferation and invasion genes and promote the expression of pro-apoptosis genes in ovarian cancer cells so as to inhibit cancer cell growth and invasion.