Fisetin, a dietary bioflavonoid, reverses acquired Cisplatin-resistance of lung adenocarcinoma cells through MAPK/Survivin/Caspase pathway

摘要

Cisplatin has been a key chemotherapy drug for treatment of non-small cell lung cancer (NSCLC) for decades. However, the efficacy of Cisplatin is usually reduced by the occurrence of drug-resistance of cancer cells. Fisetin is a flavonol naturally found in many fruits and vegetables, which has been reported to suppress cell proliferation and induce apoptosis in various cancers. In this study, we aimed to investigate whether Fisetin was capable of enhancing cytotoxicity of Cisplatin in Cisplatin-resistant NSCLC cells, and explore the possible signaling pathways involved. Cisplatin-resistant NSCLC cells, A549-CR, was established by repeated subculturing of A549 cells with increasing Cisplatin. Proliferation ability was assessed by MTT analysis and apoptosis was detected by flow cytometry. The results showed that Fisetin effectively increased sensitivity of A549-CR cells to Cisplatin, possibly mediated by inhibiting aberrant activation of MAPK signaling pathways. This increases the possibility of Fisetin as a promising agent for lung cancer therapy.