丹参酮Ⅱ_A逆转人ER阳性乳腺癌细胞的恶性表型及其机理  

Reversal of the malignant phenotypes by tanshinone Ⅱ_A in human breast cancer MCF-7 cell lines and its molecular mechanism

作　　者：杜睿[1] 郑鸿[1] 王艳萍[1] 袁淑兰[1] 

机构地区：[1]四川大学华西医院肿瘤分子诊断研究室,四川成都610041

出　　处：《华西药学杂志》2009年第1期35-38,共4页West China Journal of Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(批准号:30472041)

摘　　要：目的证实丹参酮IIA对体外培养的雌激素受体(ER)阳性人乳腺癌细胞(MCF-7)的增殖抑制及恶性表型的逆转作用;探讨其作用的分子机理。方法用光镜、电镜观察丹参酮IIA处理前后细胞形态的改变;细胞增殖试验(MTT法)、集落形成试验检测丹参酮IIA对MCF-7细胞生长、增殖的影响;RT-PCR技术半定量检测细胞增殖、分化相关基因mRNA表达的改变;流式细胞仪定量检测细胞增殖、分化相关基因蛋白表达的改变。结果经一定浓度丹参酮IIA处理后MCF-7细胞形态改变,接近正常上皮细胞形态;丹参酮IIA对MCF-7细胞增殖抑制作用具有明显的剂量-时间依赖关系;对MCF-7细胞增殖具抑制作用;可上调增殖、分化相关基因ERα、nm23-1、c-fos的表达,下调c-myc的表达。结论丹参酮IIA对MCF-7细胞体外生长、增殖有明显抑制作用;对MCF-7细胞形态具有恶性表型逆转作用;可上调细胞ERα、c-fos、nm23-1和下调c-myc基因表达,可能通过调控细胞增殖和分化相关基因的表达来逆转肿瘤细胞的恶性表型。OBJECTIVE To confirm the growth inhibition and reversal effect of the malignant phenotypes of tanshinone ⅡA in human breast cancer cells with estrogen receptor （ ER ） positive, and to elucidate its molecular mechanism of activity. METHODS Cell growth and proliferation were measured by MTT assay and colony - forming assay. The morphological characteristics of the cells treated by tanshinone ⅡA were detected by light and transmission electron microscopy. The mRNA expression of cell proliferation and differen- tiation - related genes were detected by Semi - quantitative RT - PCR technology. The protein expression of cell proliferation and differ- entiation- related genes were analyzed with quantitative flow cytometry. RESULTS Light microscopy and transmission electron microscopy showed that the configuration and ultrastructure of MCF - 7 cells had undergone restorative changes similar to that of normal epithelia after tanshinone ⅡA treatment. The MTT assay results showed that tanshinone ⅡA inhibited the cell proliferation and the inhi- bition effect had a significant dose - and time - dependent relationship. The colony - forming assay results showed that the colony - forming rates were obviously inhibited by tanshinone ⅡA. The flow cytometry and RT - PCR results showed that the expression of ER, c - los, nm23 - 1 genes were down - regulated and c - myc gene up - regulated. CONCLUSION Tanshinone ⅡA had obvious inhibi- tion effects on the growth and proliferation of MCF - 7 cells, reverse the cellular malignant phenotypes, up - regulate the expression of ERa, fos, nm23 - 1 gene and down - regulate c - myc. The mechanism of tanshinone ⅡA reversing the malignant phenotypes of tumor cells may be associated with regulation of the expression of proliferation and differentiation - related genes.

关 键 词：丹参酮ⅡA 人乳腺癌MCF-7细胞 逆转 雌激素受体 作用机理 

分 类 号：R96[医药卫生—药理学]