Gene transfer of Endostatin and K1-5 suppresses the growth of hepatocellular carcinoma

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We investigated anti-tumor effect of endostatin and K1-5, potent anti-angiogenc factors. We used KYN-2 cells, a human hepatoma cell line. KYN-2 cells(2 ×10^6 cells)were implanted in the liver of nude mice. Seven days after implantation, 100 μg of endostatin cDNA and K1-5 cDNA were transferred via tail vein by liposome method twice a week for 3weeks. For control mice, empty plasmid was injected. At day 28, the mice ware killed and tumor volume was calculated as length x width^2 × 0.52.Of endostatin treated group, tumor growth was not observed in 2 of 6 cases. Average tumor volume was 69.5 ± 76mm^3. Of K1-5 treated group, tumor growth was not observed in 3 of 6 cases. Average tumor volume was 69.5 ± 76mm^3. On the otherhand, tumor development was detected in every case of control group. Average tumor volume was 2175 ± 1386mm^3(p<0.05). The expression of endostatin and K1-5 proteins was detected in pulmonary epithelial cells, hepatocytes, and hapatoma cells, respectively.In addition, we investigated anti-tumor effect of adenovirus-mediated gene transfer of endostatin. Adenovirus-endostatin (1.5×10^9) was injected into the peritoneal cavity of nude mice 7days after implantation of KYN-2 cells (2 × 10^6 cells)into the liver. At day 28, mice ware killed and tumor volume was calculated. In endostatin treated group, average tumor volume was 180± 129mm^3. In control group, average tumor volume was 1797± 1228mm^3(p<0.05). These findings indicate that the gene therapy with endostatin and K1-5, potent anti-angiogenc factors significantly suppresses the growth of hepatocellular carcinoma.