Tum-5基因对肝细胞癌生长的抑制作用和对血管生成的影响

doi:10.13481/j.1671-587x.20180111

摘要/Abstract

摘要： 目的：探讨肿瘤抑素5（Tum-5）基因对肝细胞癌的抑制作用及对血管生成的影响，阐明其参与抗肿瘤生成的作用机制。方法：体外实验选择人肝癌HepG-2细胞，采用不同感染复数（MOI）（0、1、5、10、25和50）的pLXSN和pLXSN-Tum-5病毒颗粒感染72h，MTT法检测各组细胞增殖率。体内构建肝癌H22荷瘤小鼠模型，分为saline组、pLXSN组和pLXSN-Tum-5组，每组5只。saline组小鼠瘤内注射生理盐水，pLXSN组和pLXSN-Tum-5组小鼠瘤内分别注射相应的病毒颗粒（MOI=5），隔日注射，共注射5次。测定各组小鼠移植瘤体积、质量和小鼠体质量，免疫组织化学法检测CD31蛋白在各组小鼠移植瘤组织中的表达，计算微血管密度（MVD）。结果：与pLXSN组比较，不同MOI pLXSN-Tum-5组的细胞增殖率差异无统计学意义（P> 0.05）；荷瘤鼠瘤内注射结束后，pLXSN-Tum-5组小鼠移植瘤体积和质量均明显小于pLXSN组和saline组（P< 0.05或P< 0.01）；免疫组织化学检测，各组小鼠移植瘤内均有形态不规则的新生血管生成，与saline组和pLXSN组比较，pLXSN-Tum-5组小鼠移植瘤组织MVD平均值明显降低（P< 0.05）。结论：Tum-5可通过抑制肝癌组织内新生血管的生成发挥抑瘤作用。

关键词: 肿瘤抑素, 逆转录病毒载体, 肝细胞癌, 血管生成

Abstract: Objective: To explore the inhibitory effect of Tum-5 gene on the tumor growth and its influence in the angiogenesis of hepatocellular carcinoma (HCC),and to illustrate its mechanism involved in anti-tumorigenesis. Methods: The human HepG₂ cells were selected in in vitro experiment and treated with different multiplicity of infection(MOI) (0,1,5,10,25 and 50) of pLXSN and pLXSN-Tum-5 virus particles for 72 h. The proliferation rates of cells in various groups were detected by MTT method.In vivo,the H22 tumor-bearing mouse models were established.The mice were divided into saline group,pLXSN group and pLXSN-Tum-5 group (n=5).The mice in saline group were intratumorally injected with normal saline,and the mice in pLXSN group and pLXSN-Tum-5 group were intratumorally injected with virus particles (MOI=5),5 times every other day.The volumes and weights of transplanted tumor and the weights of mice in various groups were measured.The CD31 expressions in transplanted tumor tissue were detected by immunohistochemical method and the microvessel density (MVD) was calculated. Results: Compared with pLXSN group,the proliferation rates of cells in pLXSN-Tum-5 group after infected with different MOI of virus particles were not significantly different (P> 0.05).The volumes and weights of transplanted tumor of the mice in pLXSN-Tum-5 group were significantly smaller than those in pLXSN group and saline group after intratumoral injection (P< 0.05 or P< 0.01).The immunohistochemical results showed that there was irregular angiogenesis in each group. Compared with saline group and pLXSN group,the mean value of MVD of the transplanted tumor tissue of the mice in pLXSN-Tum-5 group was significantly decreased (P< 0.05). Conclusion: Tum-5 can exert its antitumor activity by inhibiting the formation of neovascularization in HCC.

Key words: hepatocellular carcinoma, retroviral vector, tumstatin, angiogenesis

中图分类号:

R735.7

历春, 关新刚, 王英楠, 徐聪睿, 盖晓东. Tum-5基因对肝细胞癌生长的抑制作用和对血管生成的影响[J]. 吉林大学学报(医学版), 2018, 44(01): 58-62.

LI Chun, GUAN Xingang, WANG Yingnan, XU Congrui, GAI Xiaodong. Inhibitory effect of Tum-5 gene on growth of hepatocellular carcinoma cells and its influence in angiogenesis[J]. Journal of Jilin University Medicine Edition, 2018, 44(01): 58-62.

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