【摘要】 目的小剂量化疗药物节律化疗是一种新型抗肿瘤化疗途径,在给药方式、毒副反应、作用机制等方面皆有别于传统化疗。文中探讨了小剂量紫杉醇节律化疗对小鼠Lewis肺癌细胞株皮下移植瘤生长的抑制及对其肿瘤血管生成的影响。方法C57BL/6小鼠皮下接种(Lewis Lung Cancer,LLC)细胞,成瘤后随机分为对照组(等渗盐水0.2 ml,腹腔注射,每天1次);小剂量紫杉醇组(紫杉醇2 mg/kg,腹腔注射,每天1次);常规剂量紫杉醇组(紫杉醇20 mg/kg,腹腔注射,第1天)。每天测量小鼠肿瘤体积。在第14天、第28天2个时间点分别取小鼠肿瘤,测定组织Evans Blue(EB)渗透浓度及肿瘤坏死率,半定量RT-PCR法测定肿瘤组织血管内皮生长因子-A(vasculav endothelial growth factor-A,VEGF-A)、血栓反应素-1(thrombosp-odin-1,TSP-1)、G蛋白信号通路调节蛋白5(regulator of G-protein signaling5,Rgs 5)基因表达水平。结果与对照组相比,小剂量紫杉醇节律化疗能够明显抑制Lewis肺癌细胞株皮下移植瘤的生长(P<0.01),优于常规剂量紫杉醇组,且肿瘤组织坏死率明显低于常规剂量组及对照组(P<0.05),而血管渗透性则明显高于常规剂量组及对照组(P<0.05)。小剂量组VEGF-A基因表达明显高于常规剂量组及对照组(P<0.05),而TSP-1及Rgs5基因表达明显低于常规剂量组与对照组(P<0.05)。结论小剂量紫杉醇节律性给药能够明显抑制Lewis肺癌细胞株体内生长,并可通过调节肿瘤组织VEGF-A、TSP-1以及Rgs5等基因表达水平影响肿瘤血管生成。更多还原

【Abstract】 Objective As a new anticancer method,metronomic chemotherapy with low-dose chemotherapeutic drugs might be different from traditional chemotherapy in administration,side-reaction and mechanisms.Our experiment was to explore the effects of the metronomic chemotherapy of paclitaxel on tumor growth and microenvironment of Lewis cells subcutaneous transplanted tumor.Methods Lewis lung cancer cells were subcutaneously injected into C57/BL6 mice to establish in vivo models,which were given paclitaxel at 2 mg/kg ip daily(low dose),paclitaxel at 20 mg/kg ip once(conventional dose) and normal saline ip daily(control group),respectively.The tumor volumes were recorded daily,and tumor samples obtained at 14 and 28 d after the treatment.Evans Blue was used as a marker for the determination of vascular permeability and rate of tumor necrosis.The expressions of vascular endothelial growth factor-A(VEGF-A),thrombospodin-1(TSP-1) and the regulator of G-protein signaling 5(Rgs 5) were examined by semi-quantitative RT-PCR.Results Compared with the conventional-dose and control groups,low-dose paclitaxel metronomic chemotherapy significantly inhibited the growth of Lewis lung cancer(P < 0.01),with higher blood perfusion and a lower rate of tumor necrosis,up-regulated the expression of VEGF-A(P < 0.05),and down-regulated the expressions of TSP-1 and Rgs 5(P < 0.05).Conclusion Low-dose metronomic paclitaxel could inhibit the growth in vivo of Lewis lung cancer,and influence tumor microvasculature by regulating the expressions of VEGF-A,TSP-1 and Rgs 5.更多还原