5-Aza-CdR增强TRAIL对胃癌细胞的抗瘤活性与caspase-8表达的关系

Enhanced TRAIL antitumor activity on human gastric cancer cells induced by 5-Aza-CdR is involved in up-regulation of caspase-8

目的 探讨 5 Aza CdR对凋亡诱导分子TRAIL抗胃癌细胞活性的影响。方法 采用MTT方法检测TRAIL蛋白的抗癌活性 ;采用RT PCR方法检测caspase 8mRNA的表达。结果 TRAIL 2 0 0ng/ml作用 72h对SGc 790 1、Kato 3和AGS胃癌细胞的生长抑制率分别为 9 83 %、11 94%和 4 0 4% ;经 5 Aza CdR处理后 ,对 3株胃癌细胞的抑制率分别提高到3 8 98%、5 2 42 %和 3 0 72 % ;用 5 Aza CdR处理后 3株胃癌细胞caspase 8mRNA表达明显增加。结论 5 Aza CdR能增强胃癌细胞对TRAIL的敏感性 ,其机制可能与caspase 8的表达上调有关。

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.