目的观察黏液瘤病毒(MYXV)对胃癌细胞的抑制作用。方法选用低分化原发性胃癌细胞(AGS)、来自腹水的转移性胃癌(SNU-1)、来自肝转移的转移性胃癌(NCL—N87)、来自淋巴结转移的转移性胃癌(KATOIII)等4种不同胃癌细胞株,采用Alamarblue分析MYXV对不同胃癌细胞株的抑制作用,采用Westernblot法检测MYXV的病毒复制蛋白(MT-7和Serp-1)在胃癌细胞中的表达,采用NCL.N87细胞株建立裸小鼠人胃癌移植瘤腹腔种植和皮下种植模型,观察MYXV对移植瘤的抑制作用,荧光显微镜下检测荷瘤小鼠体内活病毒。结果MYXV对4种不同胃癌细胞株都有抑制作用,抑制作用的比率分别为31.30%、33.98%、53.09%和50.12%,与对照组NIH3T3比较差异有统计学意义(P〈0.05)。病毒复制蛋白MT-7和Serp-1蛋白在所有4种胃癌细胞中都有表达。MYXV可明显抑制移植瘤的生长,肿瘤抑制率达80%,与对照组比较差异有统计学意义(P〈0.05)。荷瘤小鼠处死后只在瘤内检测到活病毒,而在其他脏器中并未检出活病毒。结论MYXV对人体胃癌具有特异性的杀伤作用而不感染正常组织和细胞,可能是一个潜在的高效安全的肿瘤治疗手段。
Objective To investigate the anti-tumor effect of myxoma virus (MYXV) on human gastric cancer. Methods Four distinct gastric cancer cell lines were employed in this study, including AGS (primary gastric cancer cell) , SNU-1 (metastatic gastric cancer cell derived from ascites), NCL-N87 (metastatic gastric cancer derived from liver), and KATO III (metastatic gastric cancer cell derived from lymph node). Alamar blue test was applied to examine the anti-tumor effect of myxoma virus on gastric cancer ceils. Western blotting was used to detect early and late viral replicate proteins, MT-7 and Serp-1. Intraperitoneal tumor model and subcutaneous tumor model were established in nude mice to investigate the in vivo anti-tumor effect of myxoma virus on gastric cancer. Results Myxoma virus exhibited anti-tumor effects on all four gastric cancer cell lines. The survival rate of four gastric cancer cells was 31.30% (AGS), 33.98% (SNU-1), 53.09% (NCL-N87) and 50. 12% ( KATO III) respectively, which was significantly higher than that of NIH3T3 ( P 〈 0. 05 ). In vivo experiment also proved that myxoma virus showed significantly higher inhibitory effect on gastric tumor growth in both intraperitoneal tumor model and subcutaneous tumor model in nude mice than control group (P 〈 0. 05 ). Conclusion Myxoma virus can spare normal cells but specifically kill human gastric cancer in vitro and in tumor nude mouse model. It might be a potential anti-tumor agent with high potency and safety.