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120μmol.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、30μmol.L-1塞来昔布作用48和72 h及60μmol.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)。120μmol.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60μmol.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。③30μmol.L-1塞来昔布作用24、48 h和60μmol.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)。120μmol.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30μmol.L-1塞来昔布组(P<0.05)。10.0 mmol.L-1阿司匹林和120μmol.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。
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^-1 aspirin groups and 30, 60 and 120μmol·L^-1 celecoxib 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 b. 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^-1 celecoxib group （48 and 72 h）, 60 μmol·L^-1 celecoxib 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^-1aspirin group after treated for 24, 48 and 72 h were higher than those of 2.5 mmol·L^-1 aspirin 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^-1 or 60μmol·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）. （2）The expressions of COX-2 and VEGF located in MCF 7 cytoplasm with yellow and pale brown staining. （3）There 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^-1 celecoxib 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^-1 aspirin for 24 and 48 h were decreased compared with those in 2.5 or 5.0 mmol·L^-1 aspirin 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^-1 aspirin or 120 μmol·L^-1 celecoxib 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.
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2009年第3期456-461,579,共7页
Journal of Jilin University：Medicine Edition
基金
吉林省科技厅白求恩医学专项基金资助课题(200705290)
作者简介
[通讯作者]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。（Tel：043-84997567，Email：wangyang@csco．org；cn）
