Effects And Mechanism Of TGF-β1/p55PIK Signaling Pathway In Proliferation Of Lung Cancer Cells

Object: We have demonstrated that p55PIK can promote DNA synthesis and cellproliferation through binding with proliferating cell nuclear antigen (PCNA) directly andfacilitating the combination of PCNA and DNA polymerase in our preliminary studies. Inthis study we aimed to investigate that TGF-β1can suppress the proliferation of lung cancercells by the regulatory effect of TGF-β1on p55PIK.Methods: Real-time analysis and immunoblotting were used respectively to determinep55PIK mRNA and the expression of p55PIK after PC-9were treated with TGF-β1.Luciferase assay was used to analyze the effect of TGF-β1on p55PIK promoter activity.The regulatory effects of TGF-β1on the signal pathway of p55PIK were determined bySi-RNA. Brdu was used to determine DNA synthesis of PC-9treated by TGF-β1,overexpressing p55PIK, or simultaneously treated by TGF-β1and overexpressing p55PIK.Results: TGF-β1could suppress mRNA, protein expression and the promoter activityof p55PIK in PC-9. The expression of p55PIK was inhibited by TGF-β1through theSmad-dependent pathway. TGF-β1suppressed proliferation of PC-9. Overexpression ofp55PIK facilitated the proliferation of PC-9and knockdown of p55PIK by Si-RNArepressed the proliferation of PC-9. Overexpression of p55PIK could partially reverse thesuppression of PC-9proliferation induced by TGF-β1. Conclusion: TGF-β1suppressed the proliferation of PC-9by inhibiting the promoteractivity, mRNA and expression of p55PIK through the Smad-dependent pathway.