Role of PTCH1 gene hypermethylation in tumorigenesis of gastric cancer / 第二军医大学学报

ABSTRACT

Objective: To study the effect of PTCH1 methylation on gastric carcinogenesis and the therapeutic effect of methylation inhibitor, 5-aza-2′-deoxyeytidine (5-aza-dC), for treatment of gastric cancer. Methods: The total RNAs were extracted from 10 gastric cancer tissues, their corresponding adjacent normal tissues, and gastric cancer cell line AGS. The PTCH1 mRNA expression was detected by Quantitative real-time PCR (QRT-PCR) and the methylation of the promoter was examined by methylation specific PCR (MSP). AGS cells were treated by 5-Aza-dC; the cell cycle and apoptosis were examined by flow cytometry, and the methylation level was also observed. Results: PTCH1 expression was negatively correlated with promoter methylation in gastric cancer tissues, their corresponding adjacent normal tissues, and gastric cancer cell line AGS (r = -0.591, P = 0.006). 5-Aza-dC treatment caused apoptosis and G 0/G1 phase arrest of AGS cells, and also induced demethylation of PTCH1 and increased its expression. Conclusion: Hypermethylation of PTCH1 gene promoter region is one of the main causes of low PTCH1 expression in AGS cells. Demethylation agent 5-Aza-dC can reverse this methylation status of PTCH1 and regulate the expression of PTCH1, suggesting a role for it in gastric cancer treatment.