Polyphyllin I suppresses proliferation and promotes apoptosis of gastric cancer cell by inhibiting stat3 phosphorylation
Jun Han, Jie Kan, Xinguo Wang, Qingling Yuan, Xiaoyan Song, Min Huang, Hao Wu
Abstract
Background: Polyphyllin I, a bioactive phytochemical extracted from Rhizoma Paridis, has been reported to exhibit anticancer activity. However, little is known about the potential of Polyphyllin I in induction of gastric cancer (GC) cell apoptosis and its underlying mechanisms. Methods: Dual-luciferase reporter assay was performed to test the bioactivity of Polyphyllin I on inhibiting JAK2/STAT3 signaling pathway. The anti-proliferation activity of Polyphyllin I was tested using cell clone formation assay. The effect of Polyphyllin I on cell cycle and apoptosis were confirmed by flow cytometry and TUNEL assay. Western blot was used to test the effect of Polyphyllin I on JAK/STAT3 pathway and apoptosis related proteins. The subcutaneous GC mouse model was established to examine whether polyphyllin I could inhibit GC growth in vivo. Results: A dual-luciferase reporter assay showed that polyphyllin I could inhibit the activity of Bcl-2 which is downstream of JAK2/STA3. Polyphyllin I significantly inhibited GC cell proliferation and induced cell apoptosis in a dose-dependent manner. The western blot results indicated that polyphyllin I mainly inhibited the phosphorylation of STAT3 by the way which is different from AG490. It was inferred that polyphyllin I may inhibit the JAK2/STAT3 pathway and affect the expression level of apoptosis related genes. Finally, in the tumor xenograft experiment proved that polyphyllin I significantly inhibited the growth of GC in vivo. Conclusions: Polyphyllin I may play its anticancer activity by inhibiting phosphorylation of STAT3 in GC cells.