Effects of PPM1 A/TGF-β1/Smads axis on the biological behavior of pan-creatic cancer PANC-1 cells
Aim:To investigate the effects of protein phosphatase magnesium dependent 1A(PPM1A)/TGF-β1/Smads axis on the biological behavior of pancreatic cancer PANC-1 cells and its possible mechanism.Methods:The expression of PPM1A in 88 cases of pancreatic cancer and 14 cases of normal adjacent pancreatic tissue from pancreatic cancer patients was detected by immunohistochemical staining with tissue microarray.The expression of PPM1A was detected by qRT-PCR and immunofluorescence assay in pancreatic cancer PANC-1,AsPC-1,BxPC-3 cells and normal pancreatic duct epithelial HPNE cells.PANC-1 cells were transfected with si-NC,si-PPM1A,pcDNA3.1 and pcDNA3.1-PPM 1A,respectively,by li-posome transfection method,CCK-8 and Transwell assays were used to detect cell proliferation,migration and invasion abili-ties,and Western blot was used to detect the expressions of TGF-β1,p-Smad2/Smad2 and p-Smad3/Smad3.CCK-8 was performed to detect whether TGF-β1/Smads signal pathway inhibitor SB431542 or activation factor TGF-β1 could reverse the promotional or inhibitory effects of si-PPM1A or pcDNA3.1-PPM1A on the proliferation in PANC-1 cells.Results;The protein expression of PPM1A in pancreatic cancer tissue was significantly lower than that in normal adjacent pancreatic tis-sue(P＜0.05).The mRNA and protein expressions of PPM1A in pancreatic cancer PANC-1,AsPC-1 and BxPC-3 cells were significantly lower than those in normal pancreatic duct epithelial HPNE cells(P＜0.05).The proliferation,migration and invasion abilities of PANC-1 cells,as well as the protein expression levels of TGF-β1,p-Smad2/Smad2 and p-Smad3/Smad3 in TGF-β1/Smads signaling pathway in si-PPM1A group were significantly higher compared with si-NC group,which were lower in pcDNA3.1-PPM1A group compared with pcDNA3.1 group(P＜0.05).SB431542 or TGF-β1 reversed the promotional or inhibitory effects of si-PPM1A or pcDNA3.1-PPM1A on the proliferation of PANC-1 cells(P＜0.05).Con-clusion;PPM1A may inhibit the proliferation,migration and invasion of pancreatic cancer PANC-1 cells by inhibiting TGF-β1/Smads signaling pathway.
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