不同治疗期Lewis肺癌小鼠血清内皮抑素与血管内皮生长因子水平变化的研究

Serum Levels of Endostatin and Vascular Endothelial Growth Factor in Different Therapy Stages of Mouse Lewis Lung Carcinoma

目的检测不同治疗时间点(治疗后当天、治疗后第5d和第19d)Lewis肺癌小鼠血清内皮抑素(mES)、血管内皮生长因子(VEGF)水平,探讨其与肿瘤发展、预后的关系。方法选择55只C57BL/6小鼠,其中11只作为健康对照组,44只复制小鼠Lewis肺癌模型后随机分为非治疗对照组、单纯化疗组、基因治疗组、联合治疗组(化疗+基因治疗),通过ELISA方法测定不同治疗时间点Lewis肺癌小鼠血清mES和VEGF的浓度,对VEGF与mES进行相关分析。结果治疗当天(第0d)4个荷瘤鼠组mES水平无明显差异。第5d基因及联合治疗组血清mES水平升高,显著高于健康对照组、非治疗对照组及单纯化疗组(P均<0.01);此后表达逐渐下降,第19d时基因及联合治疗组与化疗组(P<0.05)及健康对照组(P<0.01)差异显著。治疗第5d时基因及联合治疗组VEGF水平明显下降,与化疗组之间有明显差异(P<0.05),非治疗对照组与三个治疗组均差异显著(P<0.05);第19d即治疗结束时,基因、联合治疗组VEGF水平较第5d虽有所回升但总体仍明显降低,化疗组、基因治疗组以及联合治疗组与非治疗对照组均存在显著差异(P<0.05)。VEGF与mES相关性分析结果显示:在基因治疗及联合治疗组呈现负相关的趋势。结论血清mES及VEGF水平可能成为肿瘤治疗的监测指标。

Objective To investigate the serum levels of endostatin and vascular endothelial growth factor （VEGF） at different therapy stages of mouse Lewis lung carcinoma, and elucidate the relation to the progress and prognosis of tumor. Methods Forty-four Lewis lung carcinoma-bearing C57BL/6 mice were randomly divided into 4 groups, ie. a non-therapy group, a chemotherapy group, a gene therapy group, and a combination therapy group （chemotherapy plus gene therapy ）. Eleven healthy mice were included as normal control group. Serum was collected on the 0^th, 5^th, 19^th day after therapy for measurement of endostatin and VEGF by ELISA. The correlations were analysed between endostatin and VEGF levels in each group. Results （ 1 ） The serum endostatin levels had no significant difference in all groups on the 0^th day, but increased significantly on the 5^th day in the gene and combination therapy groups than those in other three groups （all P 〈0. 01 ）. Then the endostatin level decreased on the 19^th day in the gene and combination therapy groups, but still higher than those in the chemotherapy group and the normal group. （2） On the contrary, serum VEGF levels of the gene and combination therapy groups decreased significantly on the 5^th day and increased little on the 19^th day, which were both significant lower than those in chemotherapy group on the 5^th and 19^th day（ all P 〈0. 05）. There were significant diferences between the three therapy groups and the non-therapy group（all P 〈0. 05）. （3） Negative correlations between VEGF and endostatin levels were revealed in the gene and combination therapy groups （r = -0. 77 and -0. 761 respectively ）. Correlation was not found in the non-therapy and chemotherapy groups. Conclusion The serum levels of endostatin and VEGF might be used as monitoring indices of antiangiogenesis therapy.