CAJ | 학술논문

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。
목적：종8충신합성혈관내피세포생장인자수체2（vascular endothelial growth factor receptor 2， VEGFR2）파향억제제중사선유효억제VEGFR2적약물，병검측기항종류효과。방법8충VEGFR2파향억제제（표기위1～8호）각배성6충농도분별작용우인제정맥혈관내피세포（ human umbilical vein endothelial cells，HUVEC）화설암세포주（Tca8113）세포，동시설치5-불뇨밀정（5-FU）위양성대조조，무약물조위공백대조조。용새서람（ MTT）법검측세포생장정황，면역세포화학법검측포화농도VEGFR2억제제조화공백대조조세포VEGFR2표체，이험증억제제대VEGFR2적작용효응。결과여공백대조조상비，양성대조조능현저억제저량충세포적생장증식（ P＜0.05），불동농도각VEGFR2파향억제제조대저량충세포생장증식적차이균무통계학의의（ P＞0.05）。면역세포화학결과현시，공백대조조Tca8113세포화HUVEC세포막상VEGFR2고표체；여공백대조조상비，포화농도불동억제제조적Tca8113세포중지유6호시제조가이현저하조세포막상VEGFR2표체（ P＝0.000），이HUVEC각조VEGFR2표체차이균무통계학의의（ P＞0.05）。결론저사VEGFR2파향억제제대인제정맥혈관내피세포화설암세포생장증식무억제작용，기중지유6호억제제능현저하조설암세포VEGFR2표체，가이작위진일보연구적후선약물。
Objective To screen effective medicine with VEGFR 2 inhibitory activity from 8 novel VEGFR2 targeted inhibitors and to determine their anti-tumor properties.Methods Two cell lines(Tca8113 cells from tongue cancer and HUVEC ) were cultured respectively in groups with 6 different concentrations of the eight inhibitors (marked No.1 to No.8).Positive control using different concentrations of 5-FU and blank control without medicine were set up simultaneously .Cell growth was measured by MTT assay .Immunocytochemistry was carried out to deter-mined VEGFR2 levels in groups with different saturated inhibitors or in blank control .Results Cell growths of both cell lines were significantly inhibited in positive control groups comparing to that in blank control ( P<0.05 );there was no significant difference in cell growth between VEGFR 2 inhibitor groups and blank control in the same cell line ( P>0.05 ) .Immunohistochemistry showed that VEGFR 2 was highly expressed on the cell membranes of Tca 8113 cells and HUVEC;comparing to blank control,only No.6 VEGFR2 targeted inhibitor decreased VEGFR2 expression on Tca8113 cells significantly ( P=0.000 ) , while all inhibitors showed no VEGFR 2 inhibition on either cell line ( P>0.05 ) .Conclusion These VEGFR2 targeted inhibitors have no proliferative inhibition on the cell lines of HUVEC and Tca8113.However, No.6 inhibitor decreases the VEGFR2 expression on Tca8113 cells significantly thus becom-ing a candidate for further study .