Growth inhibition of human hepatocellular carcinoma xenograft in nude mice by combined treatment with human cytokine-induced killer cells and chemotherapy
Shi, M.; Yao, L.; Wang, F-Sheng.; Lei, Z-Yun.; Zhang, B.; Li, W-Liang.; Liu, J-Chao.; Tang, Z-Rong.; Zhou, G-de.
Zhonghua Zhong Liu Za Zhi 26(8): 465-468
2004
ISSN/ISBN: 0253-3766 PMID: 15555334 Document Number: 575150
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), lL-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 107 and 6 x 107, group 2 and 3), mitomycin-C (MMC 80 mug 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.