Enhanced TRAIL antitumor activity on human gastric cancer cells induced by 5-Aza-CdR is involved in up-regulation of caspase-8 / 第三军医大学学报

ABSTRACT

Objective To study the effects of demethylation agent 5-Aza-2′-deoxycytidine (5-Aza-CdR) on the antitumor activity of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) against gastric carcinoma. Methods Expression of caspase-8 mRNA was examined by RT-PCR. Antitumor activity of TRAIL protein was measured by MTT method. Results The inhibition rates of treatment with 200 ng/ml TRAIL for 72 h on gastric cell lines SGc 7901, Kato 3, and AGS were 9.83%, 11.94%, and 4.04%. After treatment with 5-Aza-CdR, the inhibition rates of 200 ng/ml TRAIL on gastric cell lines increased to 38.98%, 52.42%, and 30.72%. Before exposure to 5-Aza-CdR, expression of caspase-8 mRNA was low and an increased expression of the caspase-8 was found in the three gastric cancer cells after treatment with 5-Aza-CdR. Conclusion Treatment with 5-Aza-CdR can increase TRAIL antitumor activity on human gastric cancer and its mechanisms might be involved in the up-regulation of caspase-8 gene.