ABSTRACT
OBJECTIVE To investigate the antitumor effect and toxicity of doxorubicin-heparinized mesoporous silicon nanoparticles drug carrier system (DOX-HMSN) on H22 hepatoma mice. METHODS An experimental animal model of H22 hepatoma mice was established. Fifty male Kunming mice were divided into five groups:model control group,HMSN 8 mg?kg-1 group,DOX-HMSN 4,8 mg?kg-1 groups, and DOX 2 mg?kg-1(once every other day)group. Continuous intravenous injection was given once a day for 14 d. Tumor was completely stripped and weighed,and tumor inhibitory rate was determined. Pathological change of tumor tissue was observed by HE staining in H22 mice. White blood cell count was performed and the thymus index and spleen index were calculated. Levels of serum creatinine (Scr),blood urea nitrogen(BUN),glutamic pyruvic transaminase(GPT)and glutamic-oxalacetic transaminase(GOT)in serum were determined. BCL-2,BAX and vascular endothelial growth factor (VEGF)expression of tumor tissue were analyzed using Western blot. RESULTS The inhibitory rate of tumor was 20.5%,40.4%,54.8%,and 67.5%,respectively,in HMSN 8 mg?kg-1 group,DOX-HMSN 4, 8 mg?kg-1 group and DOX 2 mg?kg-1 group(P<0.01). HE results showed that HMSN 8 mg?kg-1,DOX-HMSN 4,8 mg?kg-1and DOX 2 mg?kg-1 induced tumor necrosis and nuclear dissolution of the tumor cells in H22 mice. The white blood cell count,thymus index and spleen index of mice were not signifi?cantly different between control group and HMSN group or DOX-HMSN 4 and 8 mg?kg-1 group. The levels of Scr and BUN of mice did not change obviously in HMSN 8 mg?kg-1or DOX-HMSN 4,8 mg?kg-1 groups. Compared with the model control group,the level of GPT and GOT of mice increased in the DOX 2 mg?kg-1group but decreased in HMSN 8 mg?kg-1 and DOX-HMSN 4 and 8 mg?kg-1 group(P<0.05). Compared with the control,the BAX/BCL-2 ratio(from 0.49 ± 0.06 to 0.79 ± 0.08,1.23 ± 0.14 and 1.04±0.14)increased but the VEGF expression of tumor(from 1.39±0.14 to 1.13±0.12,0.75±0.08 and 0.94 ± 0.09)decreased significantly in DOX-HMSN 4,8 mg?kg-1 and DOX 2 mg?kg-1 group(P<0.05). CONCLUSION DOX-HMSN can inhibit the tumor growth of H22 tumor-bearing mice and its antitumor mechanism might be related to inducing tumor cell necrosis and apoptosis and inhibiting tumor angiogenesis.