Telocinobufagin Has Antitumor Effects in Non-Small-Cell Lung Cancer by Inhibiting STAT3 Signaling

Non-small-cell lung carcer (NSCLC), the main histological subtype of lung cancer, is responsible for significant morbidity and mortality worldwide. Telocinobufagin, an active compound of the Chinese traditional medicine ChanSu, has antitumor effects, but its mechanism of action remains unknown. Therefore, we investigated the effect of telocinobufagin on NSCLC growth and metastasis and its possible mechanism of action, in vitro and in vivo. Cell proliferation, migration, and apoptosis were measured by methyl thiazol tetrazolium assay, colony formation, 5-ethynyl-2'-deoxyuridine incorporation, Transwell migration, wound healing, and flow cytometry analysis. A mouse xenograft model was used to evaluate tumor formation in vivo. Telocinobufagin was found to suppress proliferation and metastasis and induce apoptosis in human NSCLC cells. Moreover, telocinobufagin was able to significantly inhibit STAT3 phosphorylation at tyrosine 705 (Y⁷⁰⁵) and its downstream targets. Additionally, telocinobufagin also impaired the IL-6-induced nuclear translocation of STAT3. Consistent with the in vitro experiments, telocinobufagin reduced the A549 xenograft tumor burden and the levels of P-STAT3^Y705, MCL1, BCL2, and cleaved PARP1 in vivo. These results support telocinobufagin as a promising STAT3 signaling inhibitor candidate for the treatment of NSCLC patients.