CD40信号对宫颈癌血管生成的影响

摘要

Objective To study the effect of CD40 signal on the angiogenesis of cervical cancer. Methods The expression of CD40 in human cervical squamous epithelium cancer cell line (SiHa) and human umbilical vein endothelial cells (HUVEC) were determined by flow cytometry (FCM). Enzyme linked immunosorbent assay (ELISA) was used to detect the secretion for vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) of SiHa and HUVEC. And agonistic anti-human CD40 monoclonal antibody(5C11) was used to active CD40 signal. The proliferation of HUVEC was analyzed by 3-(4,5)-dimethylthna 20(-z-yl)-2, 5-diphernyltetra zolium bromide (MTT) reduction assay after treating with 5C11 and SiHa. Results SiHa and HUVEC cell lines both highly expressed CD40,their expression rates were 91. 3% and 91. 1% respectively. SiHa can autocrine VEGF and IL-6, and 5C11 can significantly increase their secretion. HUVEC can autocrine VEGF and IL-6,but,5C11 had no effect on their secretion. 5C11 had no effect on the proliferation of HUVEC, while SiHa can significantly promote the proliferation of HUVEC and 5C11 combined with SiHa can much more significantly promote the proliferation of HUVEC. Conclusion Human cervical cancer cell can autocrine VEGF and IL-6,and CD40 signal can increase their secretion. CD40 signal may promote the proliferation of vascular endothelial cell by increasing the secretion of VEGF and IL-6 in cervical cancer. The CD40 signal may play an important role in the angiogenesis of cervical cancer.%目的 探讨CD40信号对宫颈癌血管生成的影响.方法 采用流式细胞术检测CD40在宫颈鳞癌细胞株(human cervical squamous epithelium cancer cell line,SiHa)及人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC)上的表达;酶联免疫吸附实验(enzyme linked immunosorbent assay,ELISA)检测CD40信号对SiHa及HUVEC分泌血管内皮生长因子(vascular endothelial growth factor,VEGF)及白细胞介素6(interleukin-6,IL-6)的影响;噻唑蓝法检测CD40信号对HUVEC增殖的影响.结果 SiHa及HUVEC细胞表面均高表达CD40.SiHa细胞能够分泌VEGF及IL-6,经激发型CD40单克隆抗体(5C11)刺激后分泌量均增加.HUVEC细胞能够分泌VEGF及IL-6,经5C11刺激后分泌量均无明显变化.5C11对HUVEC的增殖无明显影响,SiHa细胞对HUVEC的生长增殖有促进作用,经5C11激发后促增殖作用更明显.结论 宫颈鳞癌细胞能够自分泌VEGF及IL-6,促进血管内皮细胞生长,CD40信号可能通过促进宫颈癌细胞分泌VEGF及IL-6来促进血管内皮细胞生长,从而介导新生血管生成,肿瘤发生浸润转移.