A serine protease extracted from Trichosanthes kirilowii inhibits epithelial-mesenchymal transition via antagonizing PKM2-mediated STAT3/Snail1 pathway in human colorectal adenocarcinoma cells
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, ChinabCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China
Trichosanthes kirilowii extract possessed various medicinal functions. Recently, it was reported that a serine protease TKP isolated from T. kirilowii inhibits human colorectal adenocarcinoma cell proliferation through inducing apoptosis. In the present study, we studied the influence of TKP on epithelial-mesenchymal transition (EMT) of human colorectal adenocarcinoma cells. The results showed that TKP suppressed EMT of both DLD1 and HCT116 cells, which was indicated by the alteration of morphology and EMT markers including E-cadherin, N-cadherin and vimentin. Consistently, cell adhesion ability was significantly declined after TKP treatment. Mechanistically, TKP treatment inhibited signal transducer and activator of transcription 3 (STAT3)/Snail1 signaling, pyruvate kinase M2 (PKM2) expression and its nuclear translocation. However, PKM2 overexpression could partially reverse the anti-EMT effect of TKP. Taken together, these results indicated that TKP inhibited EMT program of human colorectal adenocarcinoma cells via antagonizing PKM2-mediated STAT3/Snail1 pathway.