The effect of miR-485-5p on cisplatin resistance of colon cancer cells / 中华老年医学杂志

ABSTRACT

Objective:To investigate the effect of miR-485-5p on cisplatin resistance of colon cancer cells through the PI3K/Akt-PAK1 signaling pathway.Methods:The LoVo/DDP cell lines were constructedand divided into an NC group(without transfection treatment), an miR-485-5p mimics group(transfected with miR-485-5p mimics), an miR-485-5p inhibitors group(transfected with miR-485-5p inhibitors), an IPA-3 group(intervention with IPA-3)and an miR-485-5p mimics+ IPA-3 group(transfection with miR-485-5p mimics andinterventionwith IPA-3), with all given 0, 3, and 5 μmol/L cisplatin treatment.Results:Among the 20 patients, the proportion of negative miR-485-5p detection was 85.0%(17/20), and the proportion of positive detection was 15.0%(3/20); the proportion of negative PAK1 detection was 20.0%(4/20), and the proportion of positive detection was 80.0%(16/20). The expression of miR-485-5p in colon cancer tissue was significantly lower than that in adjacent tissues( P<0.05); the expression of miR-485-5p in the human colon cancer cell lines LoVo, SW620, HCT116, and SW480 was all lower than in normal intestinal mucosal cells( P<0.05); the expression of miR-485-5p in LoVo/DDP was significantly lower than inLoVo( P<0.001). Under the action of 3 μmol/L and 5 μmol/L cisplatin, LoVo/DDP had highercell viability but a lower apoptosis rate than LoVo( P<0.001). The cell survival rate in the miR-485-5p mimics group was significantly lower than that in the miR-485-5p inhibitors group( P<0.001). Compared with the NC mimics group, overexpression of miR-485-5p significantly down-regulated luciferase activity of the wild-type PAK1 reporter gene( P<0.001); P-PI3k, P-Akt and PAK1levels in the miR-485-5p mimics group were significantly lower than in the miR-485-5p inhibitors group( P<0.001); the cell survival rate in the miR-485-5p mimics group, the IPA-3 group and the miR-485-5p mimics+ IPA-3 group was significantly lower than in the NC group( P<0.001)and the cell survival rate in the miR-485-5p mimics+ IPA-3 group was significantly lower than in the miR-485-5p mimics group( P<0.001). Conclusions:Up-regulation of miR-485-5p reverses colon cancer cisplatin resistance through the PI3K/Akt-PAK1signaling pathway, suggesting that overexpression of miR-485-5p or inhibition of the PI3K/Akt-PAK1signaling pathway enhances the therapeutic efficacy of cisplatin in colon cancer.