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摘要
Background. Integrin alpha V beta 3 plays a critical role in tumour angiogenesis and metastasis formation, and is recognized as a key therapeutic target in the treatment of cancer.
Aim. To investigate whether antisense alpha V and beta 3 gene therapy has utility in the treatment of hepatocellular carcinomas. Methods. Antisense expression plasmids targeting integrin alpha V or beta 3 were constructed, and examined by immunohistochemistry and Western blot analyses for their ability to inhibit alpha V and beta 3 expression. The antisense alpha V and beta 3 expression vectors, either alone or in combination, were injected into HepG2 hepatomas established subcutaneously in nude mice and tumour growth, angiogenesis and apoptosis were monitored.
Results. Antisense alpha V and beta 3 downregulated the alpha V and beta 3 subunits expressed by human umbilical vein endothelial cells, and the alpha V subunit expressed by HepG2 cells. Gene transfer of antisense alpha V and beta 3 expression vectors downregulated alpha V and 03 in HepG2 tumours established in nude mice, inhibited tumour vascularization and growth, and enhanced tumour cell apoptosis. Antisense alpha V suppressed tumour growth more strongly than antisense beta 3; however antisense therapy that simultaneously targeted both integrin subunits was more effective than the respective monotherapies. Antisense alpha V and beta 3 inhibited tumour angiogenesis to similar extents, by a process that is independent of vascular endothelial growth factor.
Conclusions. Antisense gene therapy targeting (alpha V integrins warrants consideration as an approach to treat hepatocellular carcinomas.
- 出版日期2007-6
- 单位山东省千佛山医院; 哈尔滨医科大学
