DUSP1 enhances the chemoresistance of gallbladder cancer via the modulation of the p38 pathway and DNA damage/repair system

DUSP1通过调节p38通路和DNA损伤/修复系统增强胆囊癌的化学耐药性

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作者:Jun Fang, Zhimin Ye, Feiying Gu, Maohui Yan, Qingren Lin, Juan Lin, Zhun Wang, Yaping Xu, Yuezhen Wang

Abstract

Cisplatin (CDDP) is a commonly used drug for gallbladder cancer (GBC) chemotherapy. However, resistance to CDDP treatment results in relapse. Therefore, there is a need for the development of more effective treatment strategies to overcome chemoresistance. Dual-specificity phosphatase 1 (DUSP1) was reported to be involved in the resistance of a number of chemotherapeutic agents and was revealed to be highly expressed in CDDP-resistant GBC cells and CDDP-treated tumor types compared with normal cells or tissues in the present study. DUSP1 was revealed to inhibit the cytotoxicity of CDDP in two GBC cell lines, SGC996 and GBC-SD. P38 mitogen-activated protein kinases may be involved in the mechanism of chemoresistance. Furthermore, the number of DNA double-strand breaks in SGC996 OE cells was reduced compared with SGC996 vector cells indicating DUSP1 may attenuate the chemotherapeutic efficiency. Due to its potency against CDDP treatment, DUSP1 may be a promising target to overcome chemoresistance in GBC therapy.

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