Metformin combined with p38 MAPK inhibitor improves cisplatin sensitivity in cisplatin‑resistant ovarian cancer

Xie,Ya; Peng,Zheng; Shi,Mingxing; Ji,Mei; Guo,Hongjun; Shi,Huirong

doi:10.3892/mmr.2014.2490

Metformin combined with p38 MAPK inhibitor improves cisplatin sensitivity in cisplatin‑resistant ovarian cancer

Authors:
- Ya Xie
- Zheng Peng
- Mingxing Shi
- Mei Ji
- Hongjun Guo
- Huirong Shi
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Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: August 14, 2014 https://doi.org/10.3892/mmr.2014.2490
Pages: 2346-2350
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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