Midazolam induces A549 cell apoptosis in vitro via the miR-520d-5p/STAT3 pathway.

A novel microRNA, miR-520d-5p, can inhibit proliferation of osteosarcoma cells, but the biological role of miR-520d-5p in lung cancer is notknown. Midazolam can induce apoptosis in many kinds of cancer cells, but there are no reportson its use in lung cancer. We investigated the roles of midazolam and miR-520d-5p in apoptosis induction in a non-small cell lung cancer (NSCLC) cell line (A549). The expression of miR-520d-5p, a signal transducer and activator of transcription 3 (STAT3) and its related protein were measured by quantitative real-time PCR and Western blot. Apoptosis of the NSCLC cells in response to midazolam was determined by MTT assay, flow cytometry, and Western blot. Midazolam significantly induced A549 cell apoptosis and modulated expression of Bcl-2, Bax, and Caspase-3. Additionally, midazolam regulated STAT3 expression in A549 cells, and the siRNA inhibited STAT3 levels, highlighting their roles in the regulation of STAT3 signaling. Midazolam combined with the miR-520d-5p mimic and inhibitor, regulated STAT3 expression and its signaling pathway. Midazolam combined with the miR-520d-5p mimic significantly induced A549 cell apoptosis. Thus, midazolam can induce apoptosis of A549 cells by targeting STAT3 via miR-520d-5p. These findings suggest that midazolam might be a putative anti-cancer approach for NSCLC therapy. IJCEP