Objective: To investigate the inhibitive effect on the growth of hepatocellular carcinoma (HCC) xenografted in nude mice by adenovirus-mediated human endostatin gene.
Methods: The expression efficiency of endostatin was examined after ECV-304 cells infected with Ad/hEndo by western blot. The hepatoma BEL-7402 cells were injected into Balb/c nude mice to detect the inhibition of Ad/hEndo on the growth of HCC xenografted in nude mice. The expression of endostatin mRNA in tumor tissue was analyzed with RT-PCR, and its distribution in vivo was also analyzed.
Results: High level expression of endostatin achieved in infected ECV-304 cells by western blot. Ad/hEndo significantly inhibited the growth of xenografted BEL-7402 tumors (F=4.061, P<0.05). The intratumoral microvessel density (MVD) decreased significantly in the treated mice (6.88+/-1.08 vs 13.60+/-1.71, t=9.216, P<0.01). The expression of endostatin mRNA in tumor tissue was detected by RT-PCR in 3 days after administration intratumorally with Ad/hEndo and almost disappeared in 7 days. Endostatin mRNA was mainly located in tumor tissue with a higher concentration than that in heart, lung, spleen and liver after Ad/hEndo administration.
Conclusion: Adenovirus-mediated human endostatin gene can be expressed efficiently in vitro and in vivo, and significantly inhibit the growth of BEL-7402 xenografted tumors in nude mice.