5-杂氮-2’-脱氧胞苷对人胃癌裸鼠移植瘤的抑瘤作用

Inhibitory effect of 5-aza-2'-deoxycytidine on human gastric cancer xenografts in nude mice

目的研究5-氮-2′-脱氧胞苷(5-aza-CdR)对人正常上皮特异-1基因(NES1)及人胃癌裸鼠移植瘤的作用,探讨其抗肿瘤效应及可能机制,寻求胃癌治疗的新途径。方法建立人胃癌移植瘤裸鼠模型,用5-aza-CdR处理裸鼠,观察移植瘤生长情况,并用MSP及免疫组织化学技术检测NES1基因的甲基化状态及蛋白表达情况。结果5-aza-CdR对人胃癌裸鼠移植瘤的生长有明显的抑制作用,用药组与对照组相比,其抑瘤率为57.44%,移植瘤体积有显著差异(P<0.01);5-aza-CdR作用后,可使NES1基因exon3去甲基化,且能使NES1蛋白表达增加。结论5-aza-CdR对人胃癌裸鼠移植瘤的抑制作用可能是因为它能使因甲基化而失活的抑癌基因NES1再转录,并诱导该基因的表达,从而抑制肿瘤细胞的生长和增殖。

Objective To observe the effect of 5-aza-2＇-deoxycytidine（5-aza-CdR）on the normal epithelial specific-1 gene （NES1） and the growth of human gastric cancer xenografts in nude mice, and to explore the possible anti-tumor mechanisms and search for new treatment for gastric cancer. Methods Human gastric caner xenograft model in nude mice was established and treated with 5-aza-CdR. The growth of xenografts in nude mice was observed, and the status of methylation and protein expression of NES1 gene were detected by M SP and immunohistochemistry respectirely. Results After treatment with 5-aza-CdR, the growth of the xenografts in nude mice was greatly inhibited （ P 〈 0.01 ）. The inhibitory rate of tumor was 57.44%. The methylated exon3 of NES1 gene was found tobe demethylated and the expression of NES1 protein also increased. Conclusion 5-aza-CdR may reactivate antioncogene （NES1） silenced by de novo methylation, therefore, inhibit the growth and proliferation of gastric cancer cells in vivo.