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Inhibitory effect of cyclophosphamide combined with irradiated haploidentical lymphocyte infusion on transplanted hepatocellular carcinoma in mice
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Abstract:
Objective : To analyze the effect of irradiated haploidentical lymphocyte infusion (HLI) following different doses of cyclophosphamide （CTX） on hepatocellular carcinoma Hepal-6 cells. Methods: Female (BABL/c×C57BL)→F1(CB6F1 H-2 b/d ) mice were subcutaneously inoculated with Hepa1-6 cells to develop a solid tumor model that was taken as recipients. The irradiated haploidentical lymphocytes were from the female (BALB/c×C3H)→F1(CC3HF1 H-2 d/k ).All the mice were divided to five groups: group PBS, group CTX 80 mg/kg+SP/irr(spleen lymphocyte/5Gy irradiated), group CTX 200 mg/kg+SP/irr, group CTX 300 mg/kg+SP/irr and group SP/irr. The tumor size was measured every 2-3 days. The chimerism was measured after HLI, and the graft-versus host disease (GVHD) was assessed. Results: The tumor was significantly suppressed in group CTX 80 mg/kg+SP/irr and group CTX 200 mg/kg+SP/irr compared with group PBS (\[1.25±0.24\] cm 3, \[1.38±0.31\] cm 3 vs \[2.03±0.24\] cm 3, P<0.01), so was the survival time （48 d \[39 d, 55 d\], 40 d \[35 d,48 d\] vs 35 d \[18 d, 39 d\], P<0.05), of which, group CTX 80 mg/kg+SP/irr got significantly different antitumor effect from the group SP/irr (\[1.25±0.24\] cm 3 vs \[1.76±0.40\] cm 3，P<0.05). GVHD was not found in any groups. The chimerism of group 80 mg and 200 mg CTX combining with HLI was lower than group CTX 300 mg combining with HLI and the disappearence time was shorter. Conclusion: Transplantation of irradiated haploidentical lymphocytes following low does of CTX can induce antitumor effect on hepatocellular carcinoma of mice. Higher doses of CTX may not increase antitumor effect.
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Project Supported:
Project supported by the Science Research Foundation of Science and Technology Bureau of Fujian Province (No. 2009Y0012)
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