Inhibition of BAMBI reduces the viability and motility of colon cancer via activating TGF-β/Smad pathway and .

Colon cancer is a highly metastatic gastrointestinal cancer. BMP activin membrane-bound inhibitor (BAMBI), as a pseudo-receptor of the tumor growth factor (TGF)-β signal transduction pathway, has previously been demonstrated to be involved in human cancers. The present study demonstrated that BAMBI-small interfering (si)RNA regulated the viability and motility of colon cancer by activating TGF-β signaling. The expression level of BAMBI was suppressed by transfecting BAMBI-siRNA into the SW480 and HT-29 colon cancer cell lines. Decreased cell proliferation and increased cell apoptosis were detected in SW480 and HT-29 cells transfected with BAMBI-siRNA. Decreased expression of proliferation marker proteins Ki67 and proliferating cell nuclear antigen and elevated expression of apoptosis marker proteins (caspases-3, -8 and -9) further verified the role of BAMBI-siRNA in inhibiting cell viability. Silencing of BAMBI strongly reduced the closing rate and the number of invasive cells compared with control group. BAMBI-siRNA additionally resulted in decreased expression of migration marker proteins matrix metalloproteinase-9 (MMP-9), MMP-14 and vascular endothelial cell growth factor. In addition, the expression of TGF-β and phosphorylated-mothers against decapentaplegic homolog (Smad) 2/3 was increased in W480 and HT-29 cells transfected with BAMBI-siRNA. Elevated expression of the downstream signaling molecule E2F transcription factor 4/5 and suppressed c-MYC were additionally detected in the BAMBI-siRNA group. Finally, the experiment in the CSC xenograft revealed that BAMBI-siRNA strongly reduced the tumor growth and tumor volume. BAMBI-siRNA inhibited hepatic metastases and the expression of metastasis-associated proteins. The upregulated expression of TGF-β signaling proteins were detected in the BAMBI-siRNA group compared with control group . Overall, the results of the present study indicated that the inhibition of BAMBI reduces the viability and motility of colon cancer and may involve activation of the TGF-β/Smad pathway and .