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目的从8种新合成血管内皮细胞生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)靶向抑制剂中筛选有效抑制VEGFR2的药物,并检测其抗肿瘤效果。方法 8种VEGFR2靶向抑制剂(标记为1~8号)各配成6种浓度分别作用于人脐静脉血管内皮细胞(human umbilical vein endothelial cells,HUVEC)和舌癌细胞株(Tca8113)细胞,同时设置5-氟尿嘧啶(5-FU)为阳性对照组,无药物组为空白对照组。用噻唑蓝(MTT)法检测细胞生长情况,免疫细胞化学法检测饱和浓度VEGFR2抑制剂组和空白对照组细胞VEGFR2表达,以验证抑制剂对VEGFR2的作用效应。结果与空白对照组相比,阳性对照组能显著抑制这两种细胞的生长增殖(P<0.05),不同浓度各VEGFR2靶向抑制剂组对这两种细胞生长增殖的差异均无统计学意义(P>0.05)。免疫细胞化学结果显示,空白对照组Tca8113细胞和HUVEC细胞膜上VEGFR2高表达;与空白对照组相比,饱和浓度不同抑制剂组的Tca8113细胞中只有6号试剂组可以显著下调细胞膜上VEGFR2表达(P=0.000),而HUVEC各组VEGFR2表达差异均无统计学意义(P>0.05)。结论这些VEGFR2靶向抑制剂对人脐静脉血管内皮细胞和舌癌细胞生长增殖无抑制作用,其中只有6号抑制剂能显著下调舌癌细胞VEGFR2表达,可以作为进一步研究的候选药物。
OBJECTIVE: To screen for drugs that effectively inhibit VEGFR2 in 8 newly synthesized vascular endothelial growth factor receptor 2 (VEGFR2) -targeting drugs and test their anti-tumor effect. Methods Eight kinds of VEGFR2 targeting inhibitors (labeled as No.1-8) were respectively formulated into six human umbilical vein endothelial cells (HUVEC) and tongue cancer cell lines (Tca8113) At the same time, 5-fluorouracil (5-FU) was set as the positive control group and no drug group as the blank control group. Cell growth was detected by MTT assay. The expression of VEGFR2 in VEGFR2 inhibitor group and blank control group was detected by immunocytochemistry to verify the effect of inhibitor on VEGFR2. Results Compared with the blank control group, the positive control group could significantly inhibit the growth and proliferation of these two cells (P <0.05). There was no significant difference in the proliferation of these two cell lines with different concentrations of each VEGFR2-targeted inhibitor group (P> 0.05). Immunocytochemistry results showed that VEGFR2 was highly expressed in Tca8113 cells and HUVECs in blank control group. Compared with blank control group, only No. 6 reagent group in Tca8113 cells with different concentrations of inhibitor could significantly down-regulate the expression of VEGFR2 (P = 0.000). There was no significant difference in VEGFR2 expression between HUVEC groups (P> 0.05). Conclusion These VEGFR2-targeted inhibitors have no inhibitory effects on the growth and proliferation of human umbilical vein endothelial cells and tongue cancer cells. Only No. 6 inhibitor could significantly down-regulate the expression of VEGFR2 in tongue cancer cells, which may serve as a candidate drug for further study.