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[摘要]
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。
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[Abstract]
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 3714%, 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.
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[基金项目]
国家自然科学基金资助项目(No. 30860328);广西教育厅科研项目(No. 200810MS059)