MiR-25 reduces PC-9 / BB 4 cell apoptosis sensitivity induced by gefitinib through downregulating BIM

Bcl-2 interacting mediator of cell death (BIM) that mediated apoptosis was found to be upregulated in drug resistant lung cancer cell line. It was showed that miR-25 significantly elevated in lung cancer tissue from non-small cell lung cancer patients. This study investigated the relationship between lung cancer drug resistance and abnormal expression of miR-25 and BIM. Drug sensitive PC-9 cells and resistant PC-9/BB4 cells were cultured in vitro and treated with gefitinib at 0.015 μM. Cell apoptosis was detected by flow cytometry. MiR-25 and BIM expressions were compared. The targeted relationship between miR-25 and BIM was confirmed by dual luciferase reporter assay. PC-9/BB4 cells treated by gefitinib at 0.015 μM were divided into six groups, including control, inhibitor NC, miR25 inhibitor, scramble-pMD18-T, BIM-pMD18-T, and miR-25 + BIM-pMD18-T. Cell viability was determined by CCK8 assay. Caspase activity was tested using spectrophotometry. MiR-25 expression in PC-9/BB4 cells was significantly higher, while BIM level was obviously lower than that in PC-9 cells. Gefitinib markedly induced PC-9 cell apoptosis and upregulated BIM expression, whereas showed poor impact on PC-9/BB4 cell apoptosis and BIM level. MiR-25 suppressed BIM expression through targeting its 3’-UTR. MiR-25 inhibitor and/or BIM overexpression significantly upregulated BIM expression, enhanced caspase-9 and caspase-3 activities, declined cell viability, and increased cell apoptosis. MiR-25 elevated, while BIM reduced in PC-9/BB4 cells. MiR-25 suppressed PC-9/BB4 cell apoptosis induced by gefitinib through targeting BIM, which may play a role in PC-9/BB4 cell drug resistance.