Chemotherapy and Radiotherapy Downregulate the Activity and Expression of DNA Methyltransferase and Enhance Bcl-2/E1B- 19-kDa Interacting Protein-3-Induced Apoptosis in Human Colorectal Cancer Cells

Bcl-2/E1B 19-kDa interacting protein 3 (BNIP3) is a proapoptotic protein whose expression level is often low in colorectal cancer (CRC) cells due to the BNIP3 gene promoter DNA methylation by DNA methyltransferase (DNMT). It is known that chemotherapy and radiotherapy suppress CRC through inducing tumor apoptosis. However, the molecular mechanisms underlying chemotherapy and radiotherapy-induced apoptosis of CRC cells are not well defined. In this study, we observed that the expression level of BNIP3 in colon cancer cells was significantly increased by treatment with therapeutic agents and radiation in vitro. The BNIP3 protein level in CRC tissues from patients who received preoperative concurrent chemotherapy was significantly higher than in those who received surgery alone. Furthermore, treatment with chemotherapeutic agents and radiation significantly decreased the DNMT1 expression level and enzymatic acReceived: December 6, 2011 Accepted after revision: November 18, 2012 Published online: January 29, 2013 Zhi-ping Li, MM Department of Abdomen Oncology, Cancer Center of West China Hospital West China Medical School, Sichuan University Guoxue Lane No. 37, Chengdu 610041 (PR China) E-Mail lizhiping620312 @ yahoo.com.cn © 2013 S. Karger AG, Basel 0009–3157/13/0586–0445$38.00/0 Accessible online at: www.karger.com/che D ow nl oa de d by : 54 .7 0. 40 .1 1 1/ 6/ 20 18 5 :3 3: 08 P M