title: Metformin combined with p38 MAPK inhibitor improves cisplatin sensitivity in cisplatin‑resistant ovarian cancer.
abstract: The aim of the present study was to determine the effects of metformin, combined with a p38 mitogen‑activated protein kinase (MAPK) inhibitor, on the sensitivity of cisplatin‑resistant ovarian cancer to cisplatin. The expression and distribution of phosphorylated p38 MAPK (P‑p38 MAPK) was confirmed in drug‑resistant and primary ovarian cancer tissues by immunohistochemistry and western blotting. A bromodeoxyuridine ELISA kit was used to analyze the effects of metformin, SB203580, a p38 MAPK inhibitor, and metformin combined with SB203580, on the cell proliferation of SKOV3/DDP cisplatin‑resistant ovarian cancer cells. The protein expression of P‑p38 MAPK was significantly higher in cisplatin‑resistant ovarian cancer, as compared with the primary ovarian cancer tissues. Metformin combined with SB203580 significantly enhanced the sensitivity of SKOV3/DDP cells to cisplatin. In conclusion, the p38 MAPK signaling pathway may be associated with cisplatin‑resistant ovarian cancer. Metformin, combined with the p38 MAPK inhibitor, significantly increased the sensitivity of SKOV3/DDP cells to cisplatin treatment.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Shi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011725:Pyridines / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D011725:Pyridines; D008687:Metformin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D002945:Cisplatin