5,4’-二-正辛烷氧基-7-二氟亚甲基异黄酮抑制人乳腺癌细胞生长和诱导凋亡的作用  

Inhibition of Growth and Induction of Apoptosis in Human Breast Cancer Cell Line by 5,4'-Di-n-octoxyl-7-gem-Difluoromethylene-Genistein in Vitro

作　　者：郑芳[1] 向其德[1] 姜浩[1] 曹建国[2] 

机构地区：[1]南华大学附属第一医院,湖南衡阳421001 [2]南华大学肿瘤研究所,湖南衡阳421001

出　　处：《吉首大学学报（自然科学版）》2008年第2期106-111,共6页Journal of Jishou University(Natural Sciences Edition)

摘　　要：目的探讨金雀异黄素(Genistein,Gen)衍生物5,4’-二-正辛烷氧基-7-二氟亚甲基异黄酮(5,4’-Di-n-octoxyl-7-gem-difluoromethylene-genistein,DOdFMG)体外抑制人乳腺癌细胞系MCF-7细胞生长和诱导凋亡作用及机制,以寻找具有开发前景的肿瘤治疗新候选药物.方法体外培养人乳腺癌细胞系(MCF-7)细胞,分别应用不同浓度的DOdFMG处理人乳腺癌细胞系(MCF-7)细胞,软琼脂克隆形成法测定DOdFMG对体外培养MCF-7细胞的锚定非依赖性增殖及生长作用的影响;PI染色流式细胞计分析(FCM)法检测DOdFMG对MCF-7细胞诱导凋亡影响.western blotting法检测蛋白激酶CK2,NF-KB蛋白表达和活性的变化,初步探讨DOdFMG抗乳腺癌作用的分子机制.结果DOdFMG对体外培养MCF-7细胞具有抑制增殖及生长作用,呈剂量依赖性.DOdFMG诱导人MCF-7细胞凋亡.WesternBlot分析结果显示:DOdFMG3.0,10.0,30.0μmol/L处理人乳腺癌MCF-7细胞24h后,比较于空白对照组,蛋白激酶CK2的表达下调12.50%,41.50%,67.30%,NF-KB的表达下调20.50%,51.47%,71.93%.DOdFMG30.0μmol/L分别处理6,12,24h后,比较于空白对照组,蛋白激酶CK2的表达下调27.73%,44.8%,65.2%,NF-KB的表达下调20.50%,49.83%,69.93%.这表明DOdFMG以时间-剂量依赖方式引起蛋白激酶CK2、NF-KB下调,与先导化合物Gen比较,DOdFMG更为有效(P<0.05).结论DOdFMG显著抑制人乳腺癌细胞系(MCF-7)细胞增殖及生长;DOdFMG可诱导人乳腺癌细胞系(MCF-7)细胞凋亡;抑制蛋白激酶CK2,下调NF-κB的表达可能是DOdFMG诱导凋亡的分子机制之一.PURPOSE To investigate the effect and mechanism of the Genistein derivative 5,4＇ - Di - n - octoxyl -7 - gem- difluoromethylene- genistein（DOdFMG） on the growth and apoptosis of human breast cancer（ MCF- 7） cells line in vitro, and provide a molecular mechanism of this effect so as to find a new candidate for tumor chemotherapy. METHODS Soft ager - colon assay was used to test colon formation inhibitory effect of MCF - 7 by DOdFMG. PI stain flow cytometry（FCM） was used to analyse the apoptosis after being treated with DOdFMG. Western blotting assay was used to detect the effect of DOdFMG on the CK2 and NF- κB protein expression level of breast cells.Results： DOdFMG significantly inhibited proliferation and growth of MCF - 7 cells in dose - dependent mariner. DOdFMG significantly induced apoptosis. Western- blotting analysis indicated that after exposures to DOdFMG3.0, 10.0,30.0μmol/L for 24h, the protein expressions of CK2 were down- regulated by 12.50 %, 41.50%, 67.30 %, the protein expressions of NF- κB were down - regulated by 20.50% ,51.47% ,71.93% respectively in comparison with the control group. After MCF-7 cells were treated with DOdFMG at 30.0 μmol/L for 6, 12 and 24 h, the protein expressions of CK2 were down - regulated by 27.73 %, 44.8 %, 65.2 %, the protein expressions of NF - κB were down - regulated by 20. 5 % ,49.83 %, 69.93 % respectively in comparison with the control group. These showed that the expressions of CK2, NF - κB were decreased in a time and dose - dependent manner after treatment with various concentrations of DOdFMG.. In comparison with the lead compound Gen, DOdFMG was more effective. CONCLUSION DOdFMG possesses a significant inhibitory effect on the cell proliferation and growth of human breast carcinoma cell（ MCF - 7） in vitro DOdFMG significantly induced apoptosis of human breast cancer （MCF - 7 ） cell line. The mechanism might be associated with down - regulation of ck2 and NF - κB.

关 键 词：乳腺癌 金雀异黄素 5 4’-二-正辛烷氧基-7-二氟亚甲基异黄酮 蛋白激酶CK2 

分 类 号：R737.9[医药卫生—肿瘤]