摘要
目的探讨携带人基质金属蛋白酶组织抑制因子（hTIMP）-1的重组腺病毒（Adh—TIMP）-1对人肝癌生长、转移、血管形成以及凋亡的作用。方法构建AdhTIMP-1感染人肝癌细胞并接种于裸鼠皮下观察其成瘤情况；建立荷瘤鼠模型，观察AdhTIMP-1对肿瘤生长的作用；计数荷瘤鼠肺转移结节；CD34免疫组织化学观察肿瘤血管生成；TUNEL法检测肝癌细胞凋亡。结果AdhTIMP-1感染的HepG2细胞成瘤量下降4倍（P〈0．01），荷瘤鼠瘤体内注射AdhTIMP-1使肿瘤生长减少45％（P〈0．01），组织血管密度减少47％（P〈0．05），肺转移结节减少70％（P〈0．01），肿瘤组织中细胞凋亡增加3倍（P〈0．05）。结论AdhTIMP-1能抑制肝癌的生长、转移及血管形成，诱导肝癌细胞凋亡，可用于肝癌基因治疗的研究。
Objective To explore the effects of overexpression of human tissue inhibitors of metalloproteinase-1 （ hTIMP-1 ） on growth, metastasis, angiogenesis, and apoptosis of human hepatocellular carcinoma （HCC） in murine models. Methods Recombinant adenoviral vector containing hTIMP-1 （ AdhTIMP-1 ） was generated previously and then the anticancer activity of AdhTIMP-1 was evaluated in BALB/c mice bearing HCC. Results Compared with the controls, preinfection of HepG2 cells by Adh- TIMP-1 resulted in an obvious inhibition of tumor establishment by 4-fold （P 〈 0.01 ）. A single local injection of AdhTIMP-1 into preestabhshed tumors significantly reduced tumor growth rates by 45% （ P 〈 0.01 ）, tumor-assieiated angiogenesis index by 47% （ P 〈 0.05 ）, and lung metastases by 〉 70% （ P 〈 0.01 ）, and showed a 3-fold increase in apoptotic tumor cells （ P 〈 0.05 ）. Conclusion AdhTIMP-1 can significantly attenuate tumor growth, decrease metastasis, inhibit angiogenesis, and induce apoptosis in HCC-bearing mice and may pave the way for further hver gene therapy.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2007年第3期290-292,共3页
Chinese Journal of Experimental Surgery
关键词
癌
肝细胞
金属蛋白酶
腺病毒
基因治疗
Carcinoma, Hepatocellular
Metalloproteinase
Adenovirus
Gene therapy
