【作者】 张清媛； 康欣梅； 赵文辉；

【Author】 Zhang Qing-Yuan Rang Xin-Mei Zhao Wen-Hui Department of Medical Oncology, Cancer Hospital, Haerbin Medical University, Heilongjiang 150040, China

【机构】 哈尔滨医科大学附属肿瘤医院肿瘤内科；

【摘要】 目的:化疗作为治疗晚期肺癌的主要方法,其毒副反应和耐药性的产生严重影响了治疗效果。近期国外研究显示,一些化疗药物的持续低剂量给药方法可增加药物靶向于肿瘤微血管的效果,并具有毒副反应小和不易产生耐药的优点,本实验将低剂量紫杉醇和抗血管生成中药人参皂甙 Rg3联合应用于荷Lewis肺癌小鼠,观察其抗肿瘤血管生成作用,抑瘤效果及毒副反应,探讨它们在治疗晚期肺癌中的应用价值。方法:以荷Lewis肺癌的C57／BL6小鼠为模型,分别应用高低剂量紫杉醇联合人参皂甙Rg3治疗,观察肿瘤生长情况和外周血白细胞计数,以免疫组织化学法测定肿瘤微血管密度(MVD),半定量RT—PCR法测定血管内皮生长因子(VEGF)mRNA表达,探讨低剂量紫杉醇联合人参皂甙Rg3对肺癌肿瘤血管生成和肿瘤生长的抑制作用。结果:低剂量紫杉醇组肿瘤生长比较缓慢,小鼠外周血白细胞数均无明显下降,联合人参皂甙Rg3组抑瘤效果更持久而稳定, 毒副反应未增加。低紫杉醇组较高紫杉醇组 MVD下降(P<0．05),与对照组比较,低紫杉醇组和人参皂甙Rg3组MVD及VEGF表达均下降,二者合用时下降更多 (P<0．05)。结论:低剂量紫杉醇与人参皂甙Rg3联合应用显示出明显的抗血管生成协同作用,抑瘤效果显著且持久, 毒副反应小。从循证医学的角度看,疗效判定的终点指标应为生存期的延长或生话质量的提高,因此,这种抗血管生成联合治疗将为肺癌治疗的临床研究提供一种新的安全有效的思路。更多还原

【Abstract】 Objective: To evaluate the efficacy of the combination of low-dose paclitaxel and ginsenoside Rg3 for the antiangiogenic and antitumor effect on lewis lung carcinoma. Methods: C57/BL6 mice bearing lewis lung carcinoma were randomized into several groups, and received low-dose paclitaxel, high-dose paclitaxel, ginsenoside Rg3 and low-dose paclitaxel combined with ginsenoside Rg3 therapy respectively. Tumor growth and peripheral white blood cell counts of mice were monitored in each group. After four weeks those tumors were resected for immunohistochemical staining to detect tumor mi-crovascular density(MVD) and RT-PCR for vascular en-dothelial growth factor(VEGF)mRNA expression. Results: During the experiment, growth delays of tumor were found in low-dose paclitaxel group, without apparent leukopenia. Tumor growth delays were more remarkable and enduring when low-dose paclitaxel was used in combination with ginsenoside Rg3. MVD of tumors were lower in continous low-dose paclitaxel therapeutic group than in high-dose paclitaxel bolus therapeutic group; Compared with control group, MVD and VEGF expression decreased in continous low-dose paclitaxel therapeutic group. When ginsenoside Rg3 was added, those indicators were much lower. Conclusion: The continous low-dose regimen of paclitaxel increases the efficacy of targeting the tumor microvasculature, and produces therapeutic activity with decreased toxicity. The effects of the low-dose schedule of paclitaxel may be further enhanced by concurrent administration of angiogenic inhibitor ginsenoside Rg3. This experiment suggests a new safe therapeutic antican-cer paradigm for controlling lung cancer, which is expected to improve quality of patient’ s life and prolong their survival.更多还原