J4 ›› 2009, Vol. 35 ›› Issue (3): 456-461.

• 基础研究 • 上一篇    下一篇

阿司匹林和塞来昔布对乳腺癌细胞MCF-7中COX-2及VEGF表达的影响

王杨1, 张岩2, 孙竹平1, 刘敏1   

  1. 1.吉林大学中日联谊医院血液肿瘤内科|吉林 长春 130021;2. 吉林省长春市中心医院 吉林硅谷医院肿瘤科|吉林 长春 130012
  • 收稿日期:2008-09-25 出版日期:2009-05-28 发布日期:2009-08-14
  • 通讯作者: 王 杨 E-mail:wangyang@csco.org.cn
  • 作者简介:王 杨(1956-)|女|吉林省长春市人|教授| 主要从事血液系统疾病及恶性肿瘤的诊治研究。
  • 基金资助:

    吉林省科技厅白求恩医学专项基金资助课题(200705290)

Effects of aspirin and celecoxib on expressions of COX-2 and VEGF in breast cancer cells MCF-7

 WANG Yang1, ZHANG Yan2, SUN Zhu-Beng1, LIU Min1   

  1. 1.Department of Hematology and Oncology,China-Japan Union Hospital,Jilin University,Changchun 130021,China;2. Department of Oncology,Jilin Gui Gu Hospital of Changchun Central Hospital,
    Changchun 130012,China
  • Received:2008-09-25 Online:2009-05-28 Published:2009-08-14

摘要:

目的:通过研究非甾体类抗炎药物(NSAIDs)阿司匹林和塞来昔布对乳腺癌细胞MCF-7增殖及环氧化酶-2(COX-2)和血管内皮生长因子(VEGF)表达的影响,探讨NSAIDs的抗肿瘤作用。方法:MCF-7细胞根据所加药物不同分为不同浓度的阿司匹林(2.5、5.0和10.0mmol·L-1)组和塞来昔布(30、60和120 μmol·L-1)组,以不含药物的培养液作为阴性对照组。MTT法检测不同时间(24、48和72h)各组细胞增殖抑制率,应用免疫组织化学SP法检测不同时间(24和48h)各组MCF-7细胞中COX-2及VEGF的表达。结果:①2.5 mmol·L-1阿司匹林作用48h、30 μmol·L-1塞来昔布作用48和72 h及60 μmol·L-1塞来昔布作用48 h细胞增殖抑制率与阴性对照组比较差异无显著性(P>0.05),其他各剂量组细胞增殖抑制率高于阴性对照组(P<0.05)。10.0 mmol·L-1阿司匹林作用24、48和72 h细胞增殖抑制率高于同一时间2.5 mmol·L-1阿司匹林组(P<0.05)。120 μmol·L-1塞来昔布作用24、48和72 h细胞增殖抑制率高于同一时间30和60 μmol?L-1塞来昔布组(P<0.05)。2.5、5.0和10.0 mmol?L-1阿司匹林作用72 h较作用24 h细胞增殖抑制率升高(P<0.05)。②MCF-7细胞中均有COX-2和VEGF蛋白表达,均定位于细胞浆,染色呈黄或棕黄色。③30 μmol·L-1塞来昔布作用24、48 h和60 μmol·L-1塞来昔布作 48 h与阴性对照组比较MCF-7中COX-2和VEGF表达差异无显著性(P>0.05),其他各剂量组细胞中COX-2和VEGF表达均低于阴性对照组(P<0.05)。10.0  mmol?L-1阿司匹林作用24和48 h细胞中COX-2和VEGF表达低于同一时间2.5和5.0 mmol·L-1阿司匹林组(P<0.05)。120 μmol·L-1塞来昔布作用24和48 h细胞中COX-2和VEGF表达低于同一时间30 μmol·L-1塞来昔布组(P<0.05)。10.0 mmol·L-1阿司匹林和120 μmol·L-1塞来昔布作用48 h较作用24 h细胞中COX-2和VEGF表达降低(P<0.05)。结论:阿司匹林和塞来昔布均有抑制乳腺癌细胞MCF-7增殖的作用,同时亦能抑制细胞中COX-2和VEGF的表达,上述抑制作用随药物浓度的增加、作用时间的延长而增强。

关键词: 非甾体抗炎药, 乳腺肿瘤, 人乳腺癌细胞MCF-7, 环氧化酶-2, 血管内皮生长因子

Abstract:

Abstract:Objective To study the anti-tumor effect of aspirin and celecoxib on breast cancer cells MCF-7 through investigating their effects on the expressions of COX-2,VEGF and proliferation of MCF-7 cells. Methods The human breast cancer cells MCF-7 were divided into 2.5,5.0 and 10.0 mmol·L-1aspirin groups and 30,60 and 120 μmol·L-1celecoxib groups,the MCF-7 cells without treatment were used as negative control group.The inhibitory rates were detected by MTT assay after MCF-7 cells were treated for 24,48,72 h. The expressions of COX-2 and VEGF in MCF-7 cells after treated for 24 and 48h were detected by immunohistochemical assay.
Results  ① There were no significant differences of the inhibitory rates of the MCF-7 cell line between 2.5 mmol·L-1 aspirin group(48 h),30 μmol·L-1celecoxib group (48 and 72 h),60 μmol·L-1celecoxib group (48 h) and control group(P>0.05),the inhibitory rates in the other groups were increased compared with control group(P<0.05). The inhibitory rates of MCF-7 cells in 10.0 mmol·L-1 aspirin group after treated for 24,48 and 72 h were higher than those of 2.5 mmol·L-1aspirin group at the same time (P<0.05). The inhibitory rates of MCF-7 cells in 120 μmol·L-1 celecoxib group after treated for 24,48 and 72 h were higher than those in 30 μmol·L-1or 60 μmol·L-1 celecoxib groups at the same time(P<0.05).The inhibitory rates of MCF-7 cells in 2.5,5.0 and 10.0 mmol?L-1  aspirin groups after treated for 72 h were higher than those of MCF-7 cells after treated for 24 h(P<0.05).②The expressions of COX-2 and VEGF located in MCF-7 cytoplasm with yellow and pale brown staining.③There were no significant differences of the expressions of COX-2 and VEGF in MCF-7 cells between 30 μmol?L-1 celecoxib group(24,48 h),60 μmol·L-1celecoxib group(48 h) and negative control group(P>0.05),the expressions of COX-2 and VEGF in MCF-7 cells in the other groups were lower than that in negative control group(P<0.05).The expressions of COX-2 and VEGF in MCF-7 cells treated with 10.0 mmol·L-1aspirin for 24 and 48 h were decreased compared with those in 2.5 or 5.0  mmol·L-1aspirin groups at the same time (P<0.05).The expressions of COX-2 and VEGF in MCF-7 cells treated with 120 μmol·L-1 celecoxib for 24 and 48 h were decreased compared with those in 30 μmol·L-1 celecoxib group at the same time(P<0.05). The expressions of COX-2 and VEGF in MCF-7 cells treated with 10.0 mmol·L-1aspirin or 120 μmol·L-1celecoxib for 48 h were decreased compared with those of MCF-7 cells treated for 24 h(P<0.05).
Conclusion Aspirin and celecoxib have inhibitory effects on the growth of human breast cancer cells MCF-7,and they can inhibit the expressions of COX-2 and VEGF in MCF-7 cells in a dose and time dependent manner.

Key words: NSAIDs, breast neoplasm, human breast cancer cell MCF-7, cyclooxygenase-2, vascular endothelial growth factor

中图分类号: 

  • R737.9