乳腺癌MCF-7细胞分泌的血管内皮生长因子诱导血管内皮细胞免疫功能抑制

doi:10.6040/j.issn.1671-7554.0.2015.798

摘要/Abstract

摘要： 目的探讨乳腺癌细胞MCF-7分泌的血管内皮生长因子(VEGF)对血管内皮细胞(VEC)的免疫抑制作用。方法人脐静脉血管内皮细胞(HUVEC)生长至70%~80%融合,随机分为Media组、T-sup组、VEGF组、SU5416组。酶联免疫吸附法(ELISA)检测各组中细胞因子VEGF、前列腺素E₂(PGE₂)、白介素-6(IL-6)和白介素-12(IL-12)表达水平,CCK-8、酶联免疫斑点测定法(ELISPOT)及流式细胞术检测Media组与T-sup组HUVEC培养上清对人外周血单个核细胞(PBMC)免疫功能的影响。结果 T-sup组VEGF、PGE₂和IL-6表达水平较Media组升高(P<0.05),IL-12水平降低(P<0.05)。T-sup组HUVEC培养上清能够促进T细胞凋亡,并抑制IFN-γ表达和CD8⁺ T细胞活化。VEGF组中VEGF、PGE₂和IL-6水平较Media组升高,IL-12水平降低,SU5416组中各因子的表达水平与Media组比较差异无统计学意义(P>0.05)。结论乳腺癌MCF-7细胞诱导VEC免疫功能抑制,其免疫抑制作用与VEGF相关。

关键词: 乳腺肿瘤, 免疫抑制, 血管内皮细胞, 血管内皮生长因子

Abstract: Objective To explore the effect of breast tumor deriving vascular endothelial growth factor(VEGF)on the immune functions of vascular endothelial cells(VEC). Methods Human umbilical vein endothelial cells(HUVEC)were divided into 4 groups: Media group, T-sup group, VEGF group and SU5416 group. The levels of VEGF, PGE₂, IL-6 and IL-12 in 24 h conditioned cultural supernatants were assayed by ELISA. Experiments of CCK-8, ELISPOT and flow cytometry were processed on peripheral blood T cells after treatment with the 24 h conditioned cultural supernatants. Results The levels of VEGF, PGE₂ and IL-6 were increased in the T-sup group, compared with those in Media group(P<0.05), and the level of IL-12 was decreased in the T-sup group(P<0.05). Compared with Media group, the conditioned media in T-sup group promoted the apoptosis of T-lymphocytes, suppressed the expression of IFN-γ, and reduced the production of IFN-γ in CD8⁺ T cells. The levels of VEGF, PGE₂ and IL-6 were increased and the level of IL-12 was decreased in the VEGF group, compared with those in Media group. But there were no statistically significant differences after the treatment of SU5416, a VEGF receptor antagonist. Conclusion Breast tumor cells suppress the immune fuctions of VEC, which is closely related with the high expression of VEGF.

Key words: Breast cancer, Vascular endothelial cells, Immune suppression, Vascular endothelial growth factor

中图分类号:

R737.9

李冉冉,张鹏飞,袁冰,房菲菲, 韩明勇. 乳腺癌MCF-7细胞分泌的血管内皮生长因子诱导血管内皮细胞免疫功能抑制[J]. 山东大学学报（医学版）, 2016, 54(2): 38-43.

LI Ranran, ZHANG Pengfei, YUAN Bing, FANG Feifei, HAN Mingyong. Breast tumor deriving VEGF induces vascular endothelial cells to suppress immune functions[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(2): 38-43.

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