奥沙利铂两种给药模式下抗肿瘤效果的体内实验对比研究

目的观察奥沙利铂（L-OHP）小剂量和常规两种给药模式下对小鼠皮下移植瘤生长的抑制作用和对血管内皮生长因子（VEGF）的表达和微血管密度（MVD）的影响。方法建立肝癌H22小鼠模型后,小鼠随机分组4组,5%葡萄糖对照组、奥沙利铂0.75 mg.kg-1和1.5 mg.kg-1组,第二天开始给予腹腔等容积注射给药,连续10 d,奥沙利铂15 mg.kg-1组,第二天腹腔给药1次。第十二天处死小鼠,计算瘤重抑瘤率,测定肿瘤标本的VEGF和MVD的表达。结果奥沙利铂1.5 mg.kg-1组肿瘤生长明显低于对照组,小鼠体重与对照组相比没有明显下降,而且瘤重抑瘤率与奥沙利铂15 mg.kg-1组没有差别（P〉0.05）,与对照组比较能明显抑制肿瘤组织中VEGF及MVD的表达。奥沙利铂15 mg.kg-1组出现体重下降及血液学副作用,不能明显抑制肿瘤组织中VEGF及MVD的表达。结论小剂量奥沙利铂的抑瘤作用明显,而且没有副作用,能够抑制肿瘤组织中VEGF表达和血管生成。

Experimental comparative study of oxaliplatin antitumor effect in low dose chemotherapy and conventional chemotherapy in vivo

Aim To observe and compare inhibition effect of oxaliplatin（L-OHP）in low dose chemotherapy and conventional chemotherapy on the growth of tumor transplanted of mouse and its effect on the expression of vascular endothelial growth factor（VEGF） and microvessel density（MVD）.Methods A mouse tumor model was set up by implanting H22 mouse liver cancer cells under the skins of mice.Fourty experimental mice were divided randomly into four groups,including control 5% glucose injection group,oxaliplatin 0.75 mg·kg-1 group and oxaliplatin 1.5 mg·kg-1 group.Since the second day,the three groups were injected introperitoneally with same amount,once a day for 10 days.Oxaliplatin 15 mg·kg-1 conventional chemotherapy group was injected introperitoneally on the second day.Body weight of mice,diameters of tumours were measured and volumes were calculated after each treatment.Some of the peripheral blood were checked to evaluate bone marrow.After 12 days,the mice were killed and the tumors were taken out and the tumor-weight-inhibiting rates calculated.Tumors were examined by using immunohistochemical staining to study the expression of VEGF and MVD.Results The weight and size of the tumors in the oxaliplatin 1.5 mg·kg-1 group was similar to that in the oxaliplatin 15 mg·kg-1 conventional chemotherapy group（P0.05）,can inhibit the expression of VEGF and MVD of tumor compared with contrast group（P0.05）.Oxaliplatin 15 mg·kg-1 conventional chemotherapy group manifest diarrhea,depression,decrease of body weight and blood side effect in the experiment.Conclusion Low dose oxaliplatin show significant inhibitory effect not only on the growth of the tumors but on the expression of VEGF and MVD.