Andrographis modulates cisplatin resistance in lung cancer via miR-155-5p/SIRT1 axis.

Abstract

Andrographis (Andro) has been identified as an anti-cancer herbal. This study was to explore its underlying regulatory routes regarding cisplatin (DDP) resistance in lung cancer. The impacts of Andro on cell viability in lung cancer cells and normal cells BEAS-2B were validated using CCK8 tests. Then, cell viability and apoptosis analysis was performed in the cells after DDP, Andro, or combined treatment. RT-qPCR was applied for evaluating miR-155-5p and SIRT1 mRNA expressions, while western blot was for evaluating SIRT1 protein expressions. Binding sites between SIRT1 and miR-155-5p were predicted on TargetScan and were confirmed using luciferase reporter assays. Xenograft animal models were established for in vivo validation of the regulatory function of Andro in lung cancer. Andro decreased the cell viability in lung cancer cells but not normal cells BEAS-2B. The combined treatment with DDP and Andro induced the lowest viability and highest apoptosis in both A549 and A549/DDP cells. MiR-155-5p expression was suppressed, and SIRT was promoted by the Andro treatment, while overexpression of miR-155-5p reversed effects of Andro in cells, which was further counteracted by SIRT1 activation. SIRT1 was verified to be a target of miR-155-5p in A549/DDP cells. Moreover, Andro synergized with DDP in mice with lung cancer via miR-155-5p/SIRT1. Andro modulates cisplatin resistance in lung cancer via miR-155-5p/SIRT1 axis.