TNP-470与IL-2对肺癌细胞诱导的血管内皮细胞增殖的抑制作用

目的：应用体外细胞培养法，探讨TNP-470对肺癌细胞诱导的血管内皮细胞增殖的影响及其机制，以及TNP-470与IL-2联合用药的效应。方法：用免疫细胞化学方法检测血管内皮细胞PCNA、VEGFR-2／Flk-1、FGFR的表达，采用阳性细胞计数法及图像分析法对结果进行分析：用流式细胞分析仪对血管内皮细胞的细胞周期进行分析。结果：TNP-470以剂量依赖方式抑制肺癌细胞条件培养液或细胞粉碎液诱导的血管内皮细胞PCNA、Flk-1、FGFR的表达（与对照组比较P〈0．05）。TNP-470与IL-2均可抑制血管内皮细胞进入S期．但两者联合应用时，其效应与各自单独应用无差异（P〉0．05）。结论：TNP-470通过降低内皮细胞表面Flk-1、FGFR的表达，抑制内皮细胞进入S期，使内皮细胞阻滞于G0／G1期途径，发挥其抑制血管内皮细胞增殖的效应：而IL-2则通过对内皮细胞的毒性或诱导凋亡作用而发挥其抑制内皮细胞增殖的效应．

Inhibition of TNP-470 and IL-2 on proliferation of vascular endothelial cell induced by pulmonary adenocarcinoma cell

Objective:To explone the influence and mechanism that TNP-470 inhibits the proliferation of vascular endotheliums induced by pulmonary adenocarcinoma cells and detect the combinative efficacy of TNP-470 and IL-2 on them.Methods:The expression of PCNA,Flk-1,FGFR of endotheliums were tested by immunocytochemical analysis,and the result was positive cell-count and image-analysis methods.The influence of TNP-470 on cell cycle of endotheliums induced by pulmonary adenocarcinoma cells was analyzed by FACScan flow cytometer.Results:TNP-470 inhibited the expression of PCNA,Flk-1 and FGFR of HUVEC induced by pulmonary adenocarcinoma cells dose-dependently compared with conditional group(P<0.05).Both TNP-470 and IL-2 can block HUVEC entering S phase,but the combinative efficacy of them is not stronger than that of it(P>0.05).Conclusion:TNP-470 can inhibit the proliferation of endotheliums relatively specially by decreasing the expression of Flk-1 and FGFR,further may inhibit the entrance of S phase by blocking them in the G0/G1 phase to play the anti-tumor efficacy;And IL-2 maybe play this efficacy by cytotoxicity to endothelium.