DNA methyltransferase inhibitor 5‐aza‐CdR enhances the radiosensitivity of gastric cancer cells

Abstract

The National Comprehensive Cancer Network guidelines recommend radiotherapy as a standard treatment for patients with a high risk of recurrence in gastric cancer. Because radiation is harmful to the surrounding organs, a radiation sensitizer might therefore be useful to decrease the side effects of patients with advanced gastric carcinoma. The aim of the current study was to clarify the effect of a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (CdR), on radiation sensitivity in gastric cancer cells. Five gastric cancer cell lines, OCUM-2M, OCUM-12, KATO-III, MKN-45, and MKN-74, were used. The effects of 5-aza-CdR with irradiation on the growth activity, cell-cycle distribution, apoptosis, and apoptosis-associated gene expression were examined. 5-aza-CdR sensitized three of five gastric cancer cell lines to radiation. A combination of irradiation and 5-aza-CdR significantly (P<0.05) decreased the growth activity compared with irradiation alone in OCUM-2M, OCUM-12, and MKN-45 cells, but not in KATO-III and MKN-74 cells. The percentage of cells in G2-M phase and the apoptotic rate with irradiation in combination with 5-aza-CdR were increased in OCUM-2M, OCUM-12, and MKN-45 cells compared with irradiation alone, but not in KATO-III and MKN-74 cells. 5-aza-CdR increased the expression of p53, RASSF1, and death-associated protein kinases (DAPK) genes compared with the control or irradiation alone. These findings suggest that 5-aza-CdR might therefore be useful as a radiation sensitizer to treat some types of gastric carcinoma. The arrest at G2-M phase and increased apoptotic rate might be partly mediated by enhanced expression of the p53, RASSF1, or DAPK gene families by 5-aza-CdR.