镰刀菌色素抑制MCF-7乳腺癌细胞增殖的机制  

Inhibitory effect of pigment produced by Fusarium sp JN158 on MCF-7 cell proliferation

作　　者：郑里翔[1,2] 蔡宇杰[1] 孟宪明[2] 徐敏娟[2] 李昌伟[1] 王巧凤[2] 王月[2] 廖祥儒[1] 

机构地区：[1]江南大学工业生物技术教育部重点实验室,江苏无锡214122 [2]江西中医药大学基础医学院,江西南昌330004

出　　处：《中国药理学通报》2014年第9期1229-1234,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81160531);国家级大学生创新创业训练计划项目(No 201210412);江苏省科技创新与成果转化(重大科技支撑与自主创新)专项引导资金(No BY2010117)

摘　　要：目的通过对镰刀菌(Fusarium sp JN158)产生色素的分离、结构的鉴定,以此筛选抗肿瘤的活性成分及其部分机制的研究,为抗肿瘤药物的开发提供新途径。方法采用HPLC分离色素,使用紫外、红外及核磁鉴定色素的结构,MTT的方法测定色素对MCF-7乳腺癌细胞增殖的影响,Western blot方法分析MCF-7乳腺癌细胞内CyclinD1、NF-κB、VEGF蛋白表达。结果镰刀菌产生的色素为6个峰,其中Ⅵ号峰化合物分子质量为382,分子式是C17H18O10,为花青苷类色素,通过查新表明该色素可能是一种新的化合物。该化合物能明显抑制MCF-7细胞的增殖(P<0.05)(IC50:1.1×10-2mmol·L-1;而阳性药物乌苯美司的IC50:10 mmol·L-1),并呈现浓度的依赖性,对正常人脐静脉内皮细胞(HUVEC)没有影响;与对照组比较,Ⅵ号化合物可明显抑制MCF-7细胞内CyclinD1、NF-κB、VEGF的基因表达(P<0.05或0.01)。结论Ⅵ号色素化合物能抑制MCF-7细胞的增殖,可能的机制是抑制CyclinD1、NF-κB、VEGF基因的表达,该化合物可能是一种非常有前景的抗乳腺癌活性的化合物。Aim To explore new ways for developing anticancer drugs by the separation of pigment from Fu-sarium species JN158 （ Fusarium sp JN158 ） , the iden-tification of its structure, the screening of anticancer components and the study of its partial mechanism. Methods Pigment separation was done by HPLC, structural analysis by UV, IR, NMR, the screening of anticancer activity by MTT. Western blot was used to analyze the protein expression of CyclinD1, NF-κB, VEGF in tumor cells. Results The results showed that the pigment from Fusarium produced a total of six different peaks, of which peak Ⅵ was the anthocya-nins. Its molecular weight is about 382, molecular for-mula is C17 H18 O10 . According to investigation, this pig-ment was probably a new compound, which could in-hibit the proliferation of MCF-7 cells markedly （ IC50：0.011mmol·L-1 ,P〈0.05;the control medicine ube-nimex IC50：10 mmol · L-1 ） in a concentration-de-pendent manner, and had no effect on human umbilical cord intravenous endotheliocyte （ HUVEC ） . The influ-ence on the gene expression of CyclinD1, NF-κB, VEGF in MCF-7 cells varied with the concentration of this compound. The Western blot results showed that VI pigment compound inhibited CyclinD1, NF-κB, VEGF gene expression （P〈0.05 or 0. 01）,compared with the control group. Conclusion The Ⅵ pigment compound from Fusarium sp JN158 could inhibit MCF-7 proliferation by inhibiting CyclinD1, NF-κB, VEGF gene expression. The compound may be a promising compound against breast cancer.

关 键 词：镰刀菌色素 分离 结构鉴定 乳腺癌细胞 细胞增殖 蛋白表达 

分 类 号：R378[医药卫生—病原生物学] R329.24[医药卫生—基础医学]