miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy

Abstract

Chemotherapy is an important treatment modality for gastric cancer, and multidrug resistance (MDR) represents a major obstacle for successful cancer chemotherapy. There is a lack of research on whether microRNA (miR)-30a regulation affects the chemosensitivity of resistant gastric cancer cells, and mechanisms underlying the effects of miR-30a on drug resistance and cell autophagy require further investigation. In the present study, the expression of miR-30a and its effects in cisplatin (CDDP)-resistant human gastric cancer cells were investigated. A CDDP-resistant variant of the SGC-7901 cell line (SGC-7901/CDDP) was established by exposing the cells to gradually increasing drug concentrations, and miR-30a expression was detected by reverse transcription-semi quantitative polymerase chain reaction (RT-sqPCR). To examine the effect of miR-30a expression in the SGC-7901/CDDP cells, miR30a mimics or negative control miRNA were transfected into the cells, and a Cell Counting Kit-8 assay was performed to analyze the chemosensitivity of the different cell groups. RT-sqPCR and western blot analysis were also used to measure MDR1 mRNA and P-glycoprotein expression, and the light chain (LC)3-II/LC3-I ratio. Furthermore, apoptosis induced by the chemotherapeutic CDDP in the different groups was assessed using flow cytometry. The results demonstrated that low expression of miR-30a was associated with chemoresistance in gastric cancer cells, and in the chemoresistant cell line SGC7901/CDDP, CDDP-induced apoptosis was weakened. Additionally, it was demonstrated that the LC3-II/LC3-I ratio was elevated in SGC7901/CDDP cells compared with chemosensitive SGC7901 cells (P<0.001), which could be attenuated by upregulating miR-30a expression (P<0.001 vs. SGC7901/CDDP control cells). These results suggested that autophagy may contribute to drug resistance in gastric cancer cells, and that the reduction of LC3-II in response to miR-30a overexpression may inhibit chemoresistance-associated autophagy in gastric cancer cells.