miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression

miR-495 通过抑制 MDR1 表达,增强 MDR 癌细胞对阿霉素和紫杉醇组合的敏感性

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作者:Zhenyou Zou, Ruyi Zou, Dan Zong, Yonghong Shi, Jinyao Chen, Jie Huang, Jiahui Zhu, Liguan Chen, Xiaoyan Bao, Yuan Liu, Weihao Liu, Wenhui Huang, Jingsang Hu, Zhi Chen, Xiaojie Lao, Chaoqun Chen, Xiaoli Huang, Yao Lu, Xueyin Ni, Daoquan Fang, Dengqiang Wu, Shuangshuang Lu, Mingzhu Jiang, Chenyang Qiu

Abstract

MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR-495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR-495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol-doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre-treatment with miR-495 before chemotherapy could improve the curative effect on MDR1-based MDR cancer.

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