奥沙利铂联合复方苦参注射液抗血管生成作用的实验研究

The research on composite radix sophora flavescentis injection combined with oxaliplatin inhibiting angiogenesis

背景与目的:肿瘤的生长、转移、复发和预后均与肿瘤血管生成密切相关。以肿瘤血管生成为靶点,开发血管生成抑制剂在抗肿瘤研究中是一个十分活跃的研究领域。近年来,研究发现某些化疗药物,在小剂量、高频率的给药方式下可以选择性地显著抑制肿瘤组织内新生血管内皮细胞的生长,使肿瘤细胞因为血供不足而生长受阻。这称为小剂量化疗或抗血管生成化疗。中医药治疗肿瘤具有独到的疗效,近年来发现许多中药制剂及中药来源的药物有抗血管新生作用。本研究旨在在国内外现有的研究基础上探讨奥沙利铂联合复方苦参注射液对体内外血管生成的抑制作用。方法:采用MTT法观察奥沙利铂(L-OHP)联合复方苦参注射液对人脐静脉内皮细胞(HUVEC)、人结肠癌LoVo细胞增殖的影响;采用transwell板,观察L-OHP联合复方苦参注射液对HUVEC迁移的影响;采用鸡胚绒毛尿囊膜(CAM)模型,观察L-OHP联合复方苦参注射液对鸡胚绒毛尿囊膜新生血管的抑制作用。结果:HUVEC和LoVo细胞对不同浓度两种药物进行联合的敏感性不同。2μg/m l奥沙利铂和25μl/m l复方苦参注射液对HUVEC增殖的抑制率分别为31.6%、32.1%,联合应用后的抑制率为54.4%,具有协同作用;0.5μg/m l奥沙利铂和6.25μl/m l复方苦参注射液具有抑制HUVEC迁移的作用,联合应用具有协同效应。奥沙利铂联合应用复方苦参注射液具有抑制鸡胚尿囊膜血管生成作用。结论:小剂量L-OHP和复方苦参注射液在体外有抑制细胞生长,在体内具有抑制血管生成作用,两者联合具有协同效应。

Background and purpose： The growth, metastasis, relapse and the prognosis of tumor are correlated with tumor angiogenesis. Therefore. target to angiogenesis and antiangiogenie therapy has become one of the hot points in cancer research field. Some chemotherapeutic drugs can inhibit the growth of new vascular endothelial cell markedly in the way of low-dose and high time administration. This is metronomic chemotherapy or antiangiogenic chemotherapy. Traditional Chinese medicine has an effect on tumor control. In recent years, we discovered that some traditional Chinese medicine have an antiangiogenic effect. This experiment aimed to study the anliangiogenetic ability of oxaliplatin combined with composite radix sophora flavescentis injection（CRSFI） in vitro and in vivo. Methods： We used MTT method to observe the influence of oxaliplatin and composile radix sophora flavescentis injection on human umbilical vein endothelial cells （ HUVEC） or LoVo proliferation. The influence of oxaliplatin and comlposile radix sophora flavescentis injection on HUVEC migration was evaluated by transwell. Chick embryo chorioallantoic membrane （CAM）model was used to check whether the neovascularization of CAM could be suppressed in vivo by them. Results： The survival rate of LoVo within the same doses of oxaliplatin and composite radix sophora flavescentis injection were higher than HUVEC. Oxaliplatin （2μg/ml） and composite radix sophora flavescentis.Injection（25μl/ml） could inhihit the prolifetation of HUVEC; the rate of inhibition were 31.6%. 32.1% respectively; the rate of the two drugs combination was 54.4%. So when combined, they had synergislic effect. There was coordinate repression to migration of HUVEC in vivo when we used oxaliplatin （0.5μg/ml） and composite radix sophora flavescentis injectin （6.25μl/ml）. They also suppressed angiogenesis of CAM in vivo. Conclusions： This experiment showed that low dose oxaliplalin comtbined with composite radix sophora flavescentis injection has anti-angiogenic synergetie. ahility in vivo and the ability of inhibiting the growth of the cells in vitro.