塞来昔布抑制人类三阴性乳腺癌裸鼠移植瘤生长的实验研究  

Effects of celecoxib on tumor growth and cell apoptosis in human triple-negative breast cancer xenografts in nude mice

作　　者：王玲[1] 单保恩[1] 刘丽宏[2] 李杰[3] 王彬[1] 

机构地区：[1]河北医科大学第四医院肿瘤研究所免疫室,石家庄050011 [2]河北医科大学第四医院血液科,石家庄050011 [3]河北医科大学第四医院医务处,050011

出　　处：《肿瘤研究与临床》2011年第11期739-742,共4页Cancer Research and Clinic

基　　金：基金项目：河北省科学技术研究与发展计划（10276167）;河北省卫生厅医学科学研究重点课题计划（20110481）

摘　　要：目的探讨塞来昔布（celecoxib）对人类三阴性乳腺癌（TNBC）肿瘤生长及细胞凋亡的影响。方法32只裸鼠于背部皮下接种人类TNBC细胞株MDA-MB-231，随机分为空白对照组及低、中、高剂量塞来昔布组（25、50、100mg·kg^-1·d^-1）。实验结束后，留取移植瘤标本，观察用药前后裸鼠肿瘤体积的变化；流式细胞术（FCM）检测肿瘤细胞凋亡率；免疫组织化学法检测NF—κB p65和p50分子的表达；Western blot法检测凋亡相关分子Caspase-3、Survivin蛋白的表达。结果塞来昔布治疗组肿瘤体积较对照组均明显减小。中、高剂量塞来昔布治疗组凋亡率分别为（13．58±3．16）％、（21．91±4．75）％，与对照组的（3．15±1．73）％相比差异有统计学意义（t=6．736，12．151，均P〈0．05），塞来昔布低、中、高剂量组p65表达阳性率分别为79．3％、46．7％、23．9％，与对照组（89．7％）相比差异有统计学意义（χ^2=3．312，10．785，15．900，均P〈0．05）。Western blot结果显示，塞来昔布治疗后肿瘤组织中Caspase-3蛋白出现了裂解片段，并且随药物浓度增加，裂解片段表达量逐渐增加。Survivin蛋白随药物浓度增加表达逐渐下调。结论塞来昔布可以诱导TNBC裸鼠移植瘤细胞凋亡，抑制肿瘤生长，其抗肿瘤作用机制可能部分与抑制p65分子以及下调Survivin蛋白表达有关。Objective To evaluate the effects of celecoxib on tumor growth and cell apoptosis in human triple-negative breast cancer （TNBC） xenografts in nude mice. Methods Human TNBC MDA-MB-231 cells were inoculated subcutaneously into BALB/c nude mice. The mice （n=32） were then randomly divided into 4 groups, the control group and the celecoxib group （receiving 25, 50, 100 mg.kg^-1.d^-1 respectively）. At the end of the study, tumor tissues were collected and tumor volume was measured. Cell apoptosis was determined by flow cytometry （FCM） analysis. NF-κB p65 and p50 protein levels were measured by immunohistochemistry. Caspase-3 and survivin protein levels were detected by western blotting. Results celecoxib at dose of 25, 50 and 100 mg.kg ^-1.d^-1 inhibited the tumor growth significantly, compared with the control group. FCM results showed that apoptotie rates were （13.58±3.16） % and （21.91±4.75） % in moderate and high dose of eelecoxib-treated group, compared with （3.15±1.73） % in control group （t = 6.736, P 〈 0.05; t = 12.151, P 〈 0.05）. p65 expressions were 79.3 %, 46.7 % and 23.9 % in low, moderate and high dose of eelecoxib-treated group, compared with 89.7 % in control group 0（2 = 3.312, P 〈 0.05; χ^2 = 10.785, P 〈 0.05; = 15.900, P 〈 0.05）. Besides, western blotting analysis demonstrated that celecoxib significantly downregulated survivin expression, while upregulated the active form of caspase-3 expression. Conclusion Celecoxib could suppress TNBC tumor growth and induce cell apoptosis, which might be partially associated with inactivation of p65 and downregulation of survivin.

关 键 词：塞来昔布 乳腺肿瘤 凋亡 NF-ΚB 动物实验 

分 类 号：R737.9[医药卫生—肿瘤]