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

Abstract

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 in vivo 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 in vivo. 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 in vitro and in vivo.