Hypermethylation of BMP1 Promoter Regulates Migration of Colon Cancer Cells by Regulating the TGF-Beta 1/Smad2 Signaling Pathway

Abstract

The infiltration and migration of colorectal cancer (CRC) cells are important factors that affect the mortality rate of CRC patients. It is essential to explore the role and mechanism of metastasis of colon cancer in clinical treatment. In this study, we show that the DNA transferase inhibitor, 5-AZA-CdR (Decitabine), affected the viability and proliferation of the CRC cell line SW480 cell, as was verified by MTT. Real-time quantitative fluorescent PCR (RT-qPCR) was used for assessing mRNA expression levels of BMP1, TGF-beta, and Smad2 in SW480 cells cultured with 5-AZA-CdR for 96 h. Expression levels of BMP1, TGF-beta, and Smad2 proteins were detected by western blotting (WB). After culturing with 5-AZA-CdR, apoptosis of SW480 cells was assessed by immunohistochemical assay for Bax and Bcl-2 expression. Transwell migration assay was used to assess the influence of reducing DNA methylation on the migration of SW480 cells. Following treatment with DNA transferase inhibitor, the cell number and viability of SW480 were reduced, their invasion and migration were inhibited, TGF-beta and Smad2 expression was decreased, and that of BMP-1, Bax, and Bcl-2 was increased. We concluded that the viability and migration of SW480 cells were inhibited by stimulating BMP1 expression, which also inhibited TGF-beta and Smad2 signaling pathways, and increased Bax and Bcl-2 expression to promote the apoptosis of SW480 cells.