αv整联蛋白拮抗剂RGD肽对乳腺癌细胞增殖侵袭能力影响的研究  

Inhibitory effects of alpha-v-integrins with a RGD peptide on proliferation and invasion of breast cancer cells in vitro

作　　者：杨婉华[1] 汪蕊[1] 陈睿[1] 马湘一[1] 王世宣[1] 卢运萍[1] 马丁[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院妇产科,武汉430030

出　　处：《肿瘤》2006年第8期728-731,共4页Tumor

基　　金：国家重点基础研究发展规划项目(编号:2002CB513100)

摘　　要：目的：研究αv整联蛋白拮抗剂RGD肽对乳腺癌细胞株MDA-MB-231、MCF-7增殖侵袭能力的影响,探讨其在肿瘤靶向性治疗中的作用机制。方法：化学合成RGD肽,免疫细胞荧光技术检测RGD肽与MDA-MB-231、MCF-7细胞结合能力；MTT法检测不同浓度RGD肽对细胞增殖能力的影响；流式细胞学检测RGD肽处理对细胞周期和凋亡的影响；Boyden小室体外侵袭实验测定RGD肽处理后细胞迁移与侵袭能力的改变。结果：RGD肽与MDA-MB-231、MCF-7细胞均有特异性结合作用,15μmoI/L及更高浓度的RGD肽作用24h后细胞增殖能力显著降低(P＜0.01),细胞凋亡明显增加,细胞阻滞于G_0/G_1期,且RGD肽对细胞体外侵袭能力有不同程度的抑制作用。结论：RGD肽作为αv整联蛋白的一种拮抗剂,不仅具有药物、基因治疗载体的导向运输功能,更具有肿瘤的直接杀伤效应,是一种理想的肿瘤靶向性治疗药物。Objective：To investigate the influence of alpha（v） integrin antagonist,RGD peptide,on proliferation and invasion of breast cancer MDA-MB-231 and MCF-7 cell lines in vitro and discuss its mechanism in tumor targeted therapy. Methods：RGD peptide was chemically synthesized. The binding of RGD peptide to two breast cancer cell lines, MDA MB231 and MCF-7 cells, were measured by immunofluorescent technology. Cell proliferation was assessed by MTT assay. Cell cycle and apoptosis were measured by flow cytometry analysis. The effects of RGD peptide on the migration and invasion of breast cancer cells were deter mined using Boyden chamber assay in vitro. Results： RGD peptide bad specific bindings to MDA MB-231 and MCF-7 cells. Treatment with RGD more than 15 mmol/L for 24 h significantly decreased the proliferation of breast cancer cells, increased apoptosis, and arrested breast cancer cells at G0/G1 phase. RGD peptide also inhibited invasiveness of breast cancer cells in vitro to different degrees. Conclusion： RGD peptide as an Alpha（v） integrin antagonist has not only targeted drug-delivering function but also direct tumor-killing effects. RGD peptide is an ideal therapeutic agent for potential tumor targeting therapy.

关 键 词：乳腺肿瘤 整合素ΑV 肽类 RGD MDA-MB-231细胞 MCF-7细胞 

分 类 号：R737.9[医药卫生—肿瘤]