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.