The Synergistic Role Of Inactivated Smad4 And Activated Kras ^G12D In Liver Metastasis Of Colon Cancer

【Object】To study The synergistic role of inactivated Smad4 and activated KrasG12D in liver metastasis of colon cancer.【Methods】Knockdown the expression of smad4 in the colon cancer cell line CT26 cells by RNAi and establish a stable CT26-Smad4KD cell line. Assess the proliferation of the CT26-Smad4KD cells and the control groups by MTT assay. Inoculate CT26-Smad4KD cells and the control groups into the anterior forelimb of Balb/c nude mice, and assess the capacity of tumorigenesis in vivo by comparing the volume of the experimental groups with that of the control groups four weeks later. Assess the capacity of cell migration between the experimental groups and the control groups by Wound-Healing Assay.【Results】The expression of smad4 has decreased by more than 85% by RNAi. Treated with TGF-β,CT26 cells proliferate much slower than the untreated cells,P<0.05, while the CT26-Smad4KD cells proliferate much faster than the control groups, P<0.05. Compared with the control groups, the volume of tumor formed by CT26-Smad4KD cells decreased by about 50%, P<0.05. In the presence of TGF-β,CT26 cells migrate faster than the cells without TGF-β, while CT26-Smad4KD cells migrate slower than the control groups.【Conclusion】TGF-βcan inhibit the proliferation of CT26 cells, but this effect can be blocked by down-regulation of Smad4. Knockdown of Smad4 can inhibit the capacity of tumorigenicity of CT26 cells in vivo. TGF-βcan induce the migration of CT26 cells, which is resisted by the decreased expression of Smad4.