Angelica Dahurica extracts improve the radiosensitivity of non-small-cell lung cancer cells via deactivating the JAK1/STAT3 axis

Objective: To investigate the effects of Angelica dahurica extract (ADE) on radiosensitivity of non-smallcell lung cancer (NSCLC) cells and the JAK/STAT pathway.Methods: The viability and radiosensitivity of NSCLC cell lines (A549, Calu-1, and H460 cells) were determined using CCK-8 and colony formation assays.Apoptosis was measured using flow cytometry.The expression and phosphorylation levels of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) were measured using Western blot.In vivo, a Calu-1 cell-derived xenograft tumor model in nude mice was constructed to determine the effect of ADE on radiosensitivity.Results: ADE treatment significantly enhanced the radiosensitivity of NSCLC cell lines, as supported by increased apoptotic rate in irradiation (IR)-induced NSCLC cells.After ADE treatment, the phosphorylation level of STAT3 in IR-induced NSCLC cells was markedly decreased.Reactivation of STAT3 by co-administration of colivelin, a STAT3 activator, abolished the radio-sensitizing effect of ADE on A549, Calu-1, and H460 cells.In vivo, the combination of ADE and radiotherapy was well tolerated and significantly inhibited tumor growth.Compared with the control group and radiation group, the radiation + ADE treatment group showed lower STAT3 phosphorylation level in the transplanted tumor tissues.Conclusion: ADE exerts radio-sensitizing effects on NSCLC cells by blocking the JAK/STAT pathway.