[Growth inhibition of human hepatocellular carcinoma xenograft in nude mice by combined treatment with human cytokine-induced killer cells and chemotherapy].

OBJECTIVE: To compare the inhibitory effects of cytokine-induced killer (CIK) cells alone, chemotherapeutic drug alone, and CIK cells combined with chemotherapeutic drug on the growth of hepatocellular carcinoma (HCC) cells transplanted in nude mice.

METHODS: Peripheral blood mononuclear cells (PBMC) collected from five healthy donors by blood cell separator were incubated in vitro to induce CIK cells in the presence of interferon-gamma (IFN-gamma), IL-2 and anti-CD3 monoclonal antibody (mAb). The phenotype of CIK cells was characterized by flow cytometric analysis. BEL-7402 HCC cells were inoculated subcutaneously to nude mice. On day 5, at the inoculation site were injected normal saline (group 1), CIK cells (3 x 10(7) and 6 x 10(7), group 2 and 3), mitomycin-C (MMC 80 microg in 0.2 ml, group 4), and CIK cells combined with MMC (group 5), respectively.

RESULTS: The percentage of CD3(+), CD3(+)CD8(+), CD3(+)CD56(+), CD25(+) cells increased from 64.0%, 28.0%, 7.8%, and 9.1% to 94.7%, 67.7%, 61.3%, and 84.0% respectively after cytokine induction. The percentage of CD3(+) and CD3(+)CD8(+) cells remained at high levels during incubation period, but that of CD25(+) and CD3(+)CD56(+) cells peaked respectively on day 7 and 13 and then declined. During the 90-day observation, the tumor formation rates were 100%, 70.0%, 80.0%, 70.0% and 66.7%; and the mouse survival rates were 10.0%, 60.0%, 40.0%, 50.0% and 75.0%, respectively from group 1 to group 5. Compared to the other groups, in the combined therapy group of mice, not only the tumor grew slowly and but also showed more marked tissue necrosis.

CONCLUSION: The growth inhibitory effect on human HCC transplanted in nude mice of combined CIK cells and MMC treatment is more potent than that of CIK cells or MMC alone.