新城疫病毒7793株抑制人结肠癌LoVo细胞裸鼠移植瘤的生长及其机制

Inhibitory effect of Newcastle disease virus 7793 strain on human colon carcinoma LoVo cell-transplanted tumors in nude mice and the possible mechanism

目的:观察新城疫病毒7793株(Newcastle disease virus 7793 strain,NDV 7793)对人结肠癌LoVo细胞裸鼠移植瘤生长的作用,并探讨其可能机制。方法:建立LoVo细胞裸鼠移植瘤模型,随机分成3组,分别静脉注射PBS、5-FU以及NDV 7793,观察各组裸鼠肿瘤的生长情况,流式细胞术检测移植瘤细胞的坏死率和凋亡率,免疫组织化学法检测移植瘤组织中Bax、Bcl-2蛋白的表达,细胞色素C试剂盒检测移植瘤组织中细胞色素C的含量,ELISA法检测移植瘤组织中TNF-α含量。结果:NDV 7793较5-FU更明显抑制LoVo细胞移植瘤的生长(抑制率50.14%vs 37.14%,P<0.05)。NDV 7793组移植瘤LoVo细胞凋亡率显著高于5-FU对照组[(28.7±1.5)%vs(1.46±0.3)%,P<0.01],且NDV 7793组诱导LoVo细胞的凋亡率和坏死率[(28.7±1.5)%vs(27.80±3.32)%]相当。NDV 7793能促进移植瘤组织中Bax蛋白的表达,对Bcl-2蛋白的表达无影响。NDV 7793可提高移植瘤组织中的细胞色素C含量[(2.28±0.68)vs(0.68±0.13)μg/μl]和TNF-α的水平[(489.6±5.2)vs(167.9±3.9)pg/ml]。结论:NDV 7793可抑制人结肠癌LoVo细胞移植瘤的生长,其机制可能与其上调Bax蛋白、细胞色素C和TNF-α的表达,以及促进肿瘤细胞凋亡有关。

Objective： To investigate the effects of Newcastle disease virus 7793 strain（NDV 7793） on the growth of human colon carcinoma LoVo cell-transplanted tumors in nude mice and the possible mechanism.Methods： Mouse models of LoVo cell-transplanted tumor were established and were randomly divided into 3 groups： intravenously injected with PBS,5-FU and NDV 7793 groups.Tumor growth was observed in different groups,the apoptosis and necrosis rates of tumor cells were detected by FCM,expressions of Bax and Bcl-2 proteins were analyzed by immunohistochemical method,cyto-C level in tumor tissues was detected by cyto-C kit,and the concentration of TNF-α in tumor tissues was examined by ELISA.Results： NDV 7793 significantly inhibited the growth of LoVo-transplanted tumors compared with 5-FU（50.14% vs 37.14%,P〈0.05）.The apoptosis rate of LoVo-transplanted tumor cells in NDV 7793 group was significantly higher than that in 5-FU group（[28.7±1.5]% vs [1.46±0.3]%）,and LoVo-transplanted tumor cells had a similar apoptosis rate and necrosis rate in NDV 7793 group（[28.7±1.5]% vs [27.80±3.32]%）.NDV 7793 enhanced the expression of Bax,but not Bcl-2,in LoVo-transplanted tumor tissues,NDV 7793 also increased the cyto-C（[2.28±0.68] vs [0.68±0.13] μg/μl） and TNF-α levels（[489.6±5.2] vs [167.9±3.9] pg/ml） in LoVo-transplanted tumor tissues.Conclusion：NDV 7793 can inhibit the growth of human colon carcinoma LoVo cell-transplanted tumors,which may be related to the up-regulation of Bax,cyto-C and TNF-α and the subsequent apoptosis of tumor cells.