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AIM:To evaluate the effect of hydroxyapatite nanoparticles (Nano HAP) by intravenous injection on the inhibition of implanted hepatic VX2 tumor growth in rabbits and cell p53/c-Myc protein expression.METHODS: 60 hepatic VX2 tumor-bearing rabbits was randomly divided into five groups. Nano HAP collosol 20 mg/kg, 40 mg/kg, 5-FU solutions 20 mg/mL, mixed liquor of 5-FU solution 20 mg/mL and Nano HAP collosol 20 mg/kg were infused by vein, normal saline conducted as the control. The general state, weight, liver function and gross tumor volume were detected dynamically.The expression of p53 and c-Myc gene protein in tumor tissue was detected by immunohistochemistry methods.RESULTS: The growth of implanted hepatic VX2 tumors was significantly inhibited in all therapy groups, 3 wk after the injection, the tumor control rates in Nano HAP collosol groups were 25.5% and 32.5% respectively,and the gross tumor volumes were obviously less than that of control group. (24.81 ± 5.17 and 22.73 ± 4.23vs 33.32 ± 5.26, P ＜ 0.05). The tumor control rate of 5-FU group was 43.7% (18.74 ± 4.40 vs 33.32 ± 5.26,P ＜ 0.05), but the general state of the animals after injection aggravated; and the adverse reaction in the drug combination group obviously decreased. Due to the effect of Nano HAP, the positive expression of tumor associated the mutated p53 and c-Myc in tumor tissue was decreased obviously compared with the control group.CONCLUSION: Nano HAP has evident inhibitory action on rabbit implanted hepatic VX2 tumor in vivo, which may be the result of decreasing the expression of the mutated p53 and c-myc, and drug combination can obviously decrease the adverse reaction of 5-FU.