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[摘要]
目的:研究三氧化二砷(As2O3)对体内抗上皮性实体瘤作用,用不同剂量As2O3治疗小鼠移植性肝癌。 方法:在50只小鼠腹腔分别注射0,2,4,6,8 μmol/g As2O3,观察急性毒性作用之后,选择1,2,3 μmol/g剂量进行抑瘤实验;80只小鼠双侧腋下移植肝癌细胞(1.5×10 6细胞), 0,1,2,3 μmol/g As2O3分别右腋下注射,每日1次,共10次。在接种肝癌细胞后第30天处死小鼠检查实体瘤大小和慢性毒性反应。结果:右侧肿瘤直接注射As2O3组明显小于左侧(P<0.05);不同剂量相比,右侧给2和 3 μmol/g As2O3肿瘤重量小于对照组(P<0.001),左侧肿瘤1和2 μmol/g组肿瘤大于对照组(P<0.05),3 μmol/g组却相反(P<0.05)。抑瘤机制是引起瘤细胞凋亡。慢性毒性作用引起肝,肾,脾损伤和血中白细胞降低。结论: As2O3在合适剂量和直接接触瘤细胞,对上皮性实体瘤将是一种有用的新疗法。应强调的是抗癌治疗中注意合适剂量和给药途径。
[Key word]
[Abstract]
Objective:To investigate the antitumor effects of arsenic trioxide (As2O3) on solid tumor in vivo, the transplanted hepatic carcinoma of mice were treated with various dosages of As2O3. Methods: After 50 mice were injected intraperitoneally with 0,2, 4, 6, 8 μmol/g As2O3 respectively for observation of acute toxicity, 1, 2, 3 μmol/g were selected for this experiment. Eighty mice were transplanted with hepatic carcinoma cells (1.5×106 cells/each side) into both subaxillae. As2O3 in 0, 1, 2 and 3 μmol/g were injected into right subaxilla respectively once every day for 10 days. At the 30th day after transplanted hepatic carcinoma cell, mice were killed and the size of solid tumors was measured. The chronic cytotoxicity of As2O3 was observed in these mice.Results:In right subaxillae tumors, which were injected directly with As2O, were apparent smaller than that in the left (P<0.05). Comparing different dosage, the right solid tumors in 2 and 3 μmol/g groups were smaller than that in control group (P<0.001). In the left the tumor masses of 1 and 2 μmol/g groups were larger than that in control group (P<0.05) and 3 μmol/g group vice versa (P<0.05). The mechanism of action of As2O3 was inducement of cellular apoptosis. The damages of liver, kidney, spleen and decrease of WBC were found by chronic toxicity of As2O3.Conclusion: Our results suggested that As2O3 in a convenient dosage and in direct contact with tumor cells might be a useful, novel therapy for epithelial solid tumor and the permissible dosage and the route of administration were emphasized in the anticancer therapy.
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[基金项目]
广东省中医药局资助科研课题(100083)