小剂量化疗联合人参皂甙Rg3抑制小鼠Lewis肺癌血管生成作用实验研究

背景与目的目前发现一些细胞毒性化疗药物小剂量、短间隙、持续给药可表现出明显的抗肿瘤血管生成作用，从而抑制肿瘤生长和转移，被称作“抗肿瘤血管生成化疗（anti-angiogenic chemotherapy）”。近来从中药人参中提制的人参皂甙Rg3也被证实具有抑制肿瘤血管生成的作用。本研究的目的是观察小剂量吉西他滨和人参皂甙Rg3联合治疗对小鼠Lewis肺癌血管生成的抑制作用，以及对小鼠生存质量的影响。方法建立小鼠Lewis肺癌模型，分别给予小剂量吉西他滨、人参皂甙Rg3以及二者的联合治疗。利用彩色多谱勒超声、免疫组化技术等观察和比较各治疗组的肿瘤血管生成和肿瘤生长情况。结果人参皂甙Rg3和吉西他滨联合治疗组小鼠有较好的生存质量。彩色超声多谱勒以及免疫组化结果发现联合治疗组比单药治疗组具有更高的肿瘤坏死率和更强的抗肿瘤血管生成作用。结论小剂量吉西他滨与人参皂甙Rg3联合治疗可能具有协同抑制肿瘤血管生成的作用，从而取得协同抗肿瘤效应，同时可维持较好的生存质量。

Anti-angiogenic effects of low-dose gemcitabine combined with ginsenoside Rg3 on mouse Lewis lung carcinoma

Background and objective The results of recent experimental studies have suggested that frequently continuous administration of certain cytotoxic agents at low doses (a tenth to a third of the maximum tolerated dose), known as 'anti-angiogenic chemotherapy', can increase the efficacy by targeting the tumor microvasculature. Ginsenoside Rg3 has also been proven to have certain anti-angiogenic effects. The aim of this study is to investigate the inhibitory effects of administration of low-dose gemcitabine combined with ginsenoside Rg3 on angiogenesis of mouse Lewis lung carcinoma and the influence of administration on quality of life of mouse. Methods A novel mouse model was developed by inoculating Lewis lung carcinoma cells directly into C57B1/6 mice. The mice were treated with low-dose gemcitabine, ginsenoside Rg3, or both agents together respectively. Then angiogenesis and growth of tumor were observed by color Doppler flow imaging (CDFI) and immunohistochemistry. Results Remarkably, the combined therapy of gemcitabine and ginsenoside Rg3 resulted in better quality of life of mice than either single agent administration. CDFI and immunohistochemistry showed that there were significantly higher tumor necrosis rate and stronger anti-angiogenic effects in combined therapy group than single agent group. Conclusion The combined therapy of low-dose gemcitabine and ginsenoside Rg3 may cooperatively inhibit neovascularization and growth of mouse Lewis lung carcinoma, and it can keep good quality of life of mouse. It may provide a new strategy for cancer therapy.