Background: Radioresistance is a huge obstacle in radiotherapy of non-small cell lung cancer (NSCLC) and how to raise radiosensitivity is an urgent issue.
Objectives: In this study, we investigated the role and molecular mechanism of sodium new houttuyfonate (SNH) in regulation of radiosensitivity of NSCLC cells.
Material and methods: The Cell Counting Kit-8 (CCK-8) was used to measure cell viabilities of NSCLC cell lines A549 and HCC827 after a treatment with SNH (0 mM, 0.1 mM and 0.3 mM). It examined cytotoxicity induced by X-ray (0 Gy, 1 Gy, 2 Gy, 4 Gy, 6 Gy, and 8 Gy) after SNH (0.3 mM) treatment, while flow cytometry was used for apoptosis detection use. Expression of miR-147a or signal transducer and activator of transcription (STAT3) in selected cell lines was assessed through real-time quantitative polymerase chain reaction (RT-qPCR). The CCK-8 was then applied to measure cytotoxicity in cells with miR-147a upregulation or STAT3 suppression under irradiation apoptosis changes were detected with flow cytometry. Thereafter, binding conditions between miR-147a and STAT3 were checked using luciferase reporter assays. Expressions of STAT3 in A549 transfected by siNC, siSTAT3, and by siSTAT3 and miR-147a mimics were checked using RT-qPCR and the phosphorylation of STAT3 was observed using enzyme-linked immunosorbent assay (ELISA).
Results: The SNH treatment significantly suppressed cell viabilities and increased apoptosis of lung cancer cells. Cytotoxicity and apoptosis in A549 cells were both enhanced after SNH treatment and raised as the dosages of X-ray grew. MiR-147a presented lower expression in lung cancer cells and was upregulated by SNH, which further contributed to higher cell apoptosis after irradiation. STAT3 directly bound miR-147a and was more expressed in NSCLC cells. Inhibited phosphorylation of STAT3 promoted apoptosis in A549 cells after X-ray exposure. Overexpressed miR-147a inactivated STAT3 signaling, adding to cell apoptosis after irradiation.
Conclusions: SNH-induced miR-147a increased radiosensitivity of A549 cells through inactivation of STAT3 pathway.
Keywords: STAT3; miR-147a; sodium new houttuyfonate.