Background:
Non-small-cell lung cancer (NSCLC) is the most common histological subtype of
lung cancer with significant morbidity and mortality rates worldwide.
Cinobufagin, the primary component of
Chansu and the major active ingredient of
cinobufacini, has attracted widespread attention for its excellent anticancer effects, but its activity remains poorly characterized in NSCLC. Methods: The functions of
cinobufagin treatment in anti-
tumor was evaluated using various in vitro and in vivo assays. The change of STAT3 signaling by
cinobufagin was analyzed using molecular docking, immunofluorescence technic and western blotting. Results: In vitro, we confirmed the inhibitory effect of
cinobufagin on cell viability, proliferation, migration, epithelial-mesenchymal transition (EMT), as well as an apoptosis-inducing effect. The antitumor effects of
cinobufagin were confirmed in vivo by measuring
tumor growth in a mouse xenograft model.
Cinobufagin was found to significantly inhibit the phosphorylation of
signal transducer and activator of transcription 3 (STAT3) at
tyrosine 705 (Y705) in a time- and concentration-dependent manner. Moreover,
cinobufagin reversed IL-6-induced nuclear translocation of STAT3. Conclusions: Our study has demonstrated that
cinobufagin exerts an antitumor effect in
non-small-cell lung cancer by blocking STAT3 signaling, and
cinobufagin is a promising candidate agent for NSCLC
therapy.