Anti-tumor Effects Of Interleukin-18 On Subcutaneous Transplantation Tumor Model Of Hepatocellular Carcinoma In BALB/c Nude Mice

Objective: To observe and explore the antitumor effects of interleukin-18 (IL-18) and its possible mechanisms by establishing subcutaneous transplantation tumor model of hepatoma in BALB/c nude mice.Methods: HepG2 cells were inoculated intradermally (i.d.) into the nude mice at concentration of 5×106 to establish tumor model, then the mice received intraperitoneally (i.p.) injection of mIL-18 for different groups every two days. There were two dependent parts in stage of treating the transplantation tumors, (1) Grouping by varied doses of IL-18(0μg , 0.75μg, 1.00μg, 1.25μg per mouse), (2) Grouping by distinct course of treatment(0 week, 2 weeks, 3 weeks, 4 weeks). During the term of treatment, the volume of tumors were measured 2 or 3 days a time. After 4 weeks treatment, the mice were killed and their tumors and livers were taken, kept for further ELISA, RT-PCR tests.Results: 1. Each nude mouse that had inoculated intradermally (i.d.) with HepG2 cells grow subcutaneous transplantation tumor in about 7 days, the rate of tumor formation is 100%; 2. In the part of grouping by dose of IL-18, the weight, volume of tumors in received treatment groups were much lighter, smaller than that of control group(P<0.05), yet among groups that received injection of IL-18 had no significant differences (P>0.05); 3. In another part of test showed that the groups which IL-18 treatment began at the same time with HepG2 or had a longer course of treatment resulted in more smaller tumor volume, lighter weight compared with later treatment and short term treatment group; 4. Immunohistochemistry test showed that expression of vascular endothelial growth factor (VEGF) were positive by tumors in each group and no significance among them, yet RT-PCR showed that there were difference between treatment groups and control group(P<0.05).Conclusion: 1.The subcutaneous transplantation tumor model of hepatocellular carcinoma in nude mice established by using HepG2 cell line may be used to study the effect and mechanism of IL-18 treatment on hepatocellular cancer, at the same time, it is a optimal animal model to study the mechanism of immunotherapy for hepatoma; 2. IL-18 may efficaciously inhibited the growth of hepatoma in nude mice at dose of 0.75μg, 1μg, 1.25μg per mouse; early treatment and longer course of treatment may be helpful. 3. The cytotoxic effects induced by natural killer cells may be one of the mechanisms through which IL-18 carry out its anti-tumor effects; IL-18 inhibited the expression of VEGF in tumors and further more suppressed angiogenesis may be another mechanism. The effect of suppression may associate with inhibition of VEGF, IL-18BP.