Cisplatin resistance in gastric cancer cells is involved with GPR30-mediated epithelial-mesenchymal transition.

Abstract

Cisplatin is the major chemotherapeutic drug in gastric cancer, particularly in treating advanced gastric cancer. Tumour cells often develop resistance to chemotherapeutic drugs, which seriously affects the efficacy of chemotherapy. GPR30 is a novel oestrogen receptor that is involved in the invasion, metastasis and drug resistance of many tumours. Targeting GPR30 has been shown to increase the drug sensitivity of breast cancer cells. However, few studies have investigated the role of GPR30 in gastric cancer. Epithelial-mesenchymal transition (EMT) has been shown to be associated with the development of chemotherapeutic drug resistance. In this study, we demonstrated that GPR30 is involved in cisplatin resistance by promoting EMT in gastric cancer. GPR30 knockdown resulted in increased sensitivity of different gastric cancer (GC) cells to cisplatin and alterations in the epithelial/mesenchymal markers. Furthermore, G15 significantly enhanced the cisplatin sensitivity of GC cells while G1 inhibited this phenomenon. In addition, EMT occurred when AGS and BGC-823 were treated with cisplatin. Down-regulation of GPR30 with G15 inhibited this transformation, while G1 promoted it. Taken together, these results revealed the role of GPR30 in the formation of cisplatin resistance, suggesting that targeting GPR30 signalling may be a potential strategy for improving the efficacy of chemotherapy in gastric cancer.

• Authors: Xiaofeng Wang, Zhiyuan Xu, Jiancheng Sun, Hang Lv, Yiping Wang, Yixiu Ni, Shangqi Chen, Can Hu, Lijing Wang, Wei Chen, Xiangdong Cheng
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 6 Pg. 3625-3633 (03 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 32052561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• GPER1 protein, human
• Receptors, Estrogen
• Receptors, G-Protein-Coupled
• Cisplatin

Topics

• Cell Line, Tumor
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Epithelial Cells (drug effects, metabolism)
• Epithelial-Mesenchymal Transition (drug effects)
• Humans
• Receptors, Estrogen (metabolism)
• Receptors, G-Protein-Coupled (metabolism)
• Stomach Neoplasms (metabolism, pathology)