Timosaponin Inhibit Proliferation and Stem Cell Formation of Lung Cancer Through Regulating Hedgehog Signaling-mediated SOX2

Abstract

Objective To explore the effects of Timosaponin (TMS) on lung cancer and cancer stem cell (CSC) and its underlying mechanism. Methods MTS, Hoechst 33342 staining, flow cytometry, cell migration and plate cloning experiments were used to detect the effect of TMS on cell biological functions. The effect of TMS on tumor ball formation was measured and confirmed by the ADELFLUOR. RT-qPCR and Western blot were applied to detect the effect of TMS on key genes and proteins in Hedgehog signaling pathway and CSC, and the effect of SMO and SOX2 protein on tumor sphere formation were evaluated by siRNA transfection. Results TMS can inhibit the proliferation of lung cancer cells and the growth of CSCs. TMS can reduce the protein expression levels of GLI1, GLI2 and SMO, and siRNA targeting SMO can inhibit the formation of tumor spheres. In addition, TMS can reduce the transcription and protein expression of SOX2, while siRNA targeting SOX2 can inhibit the formation of tumorspheres. TMS inhibited the formation of lung CSC by regulating the expression of GLI1, GLI2, SMO, and SOX2. Conclusion TMS could regulate Hedgehog signaling pathway-mediated SOX2 to suppress the formation of lung cancer stem cells, thereby inhibiting the proliferation and migration of lung cancer cells, which lays the foundation for targeting Hedgehog signaling pathway and SOX2 in the treatment of lung cancer.

Keywords

• lung cancer
• stem cells
• timosaponin
• hedgehog signaling pathway
• sox2