Desmosdumotin-C B环衍生物抑制MCF-7细胞增殖及其作用机制研究  

Inhibitory effect and mechanism of Dsmosdumotin-C B ring derivative on MCF-7 cell proliferation

作　　者：郭宏举 常李荣[1] 史宁[1] 张捷[1] 向卓[2] 梁海[1] 吴久鸿[1] 

机构地区：[1]解放军第306医院药学部,北京100101 [2]解放军第401医院药剂科,青岛266071

出　　处：《药物评价研究》2017年第2期179-183,共5页Drug Evaluation Research

基　　金：国家自然科学基金项目(81072546;81470156)

摘　　要：目的研究desmosdumotin-C(Des-C)B环对位氟修饰衍生物TPP对人乳腺癌细胞MCF-7的增殖抑制作用,并探讨其作用机制。方法 MTT法检测质量浓度为1.0、2.5、5.0、10.0、20.0μg/m L的TPP作用48 h后,对MCF-7细胞的增殖抑制率;流式细胞术检测20.0μg/m L TPP作用0、24、48 h诱导MCF-7细胞的凋亡程度;流式细胞术检测20.0μg/m L TPP作用0、24、48 h对MCF-7细胞中NF-κB P65阳性细胞表达率的影响。结果作用48 h后,2.5、5.0、10.0、20.0μg/m L的TPP对MCF-7细胞增殖均有显著抑制作用,且抑制率随着浓度的升高而增大;20μg/m L TPP作用24、48 h均可诱导细胞凋亡;作用48 h后,20μg/m L TPP可显著减少MCF-7中NF-κB P65阳性细胞率。结论 TPP显著抑制MCF-7细胞增殖,诱导MCF-7细胞凋亡,作用机制可能与下调NF-κB表达有关。Objective To study the inhibitory effects of TPP, a desmosdumotin-C B ring para-fluoro modified derivative, on human breast cancer MCF-7 cell proliferation, and investigate the possible mechanisms. Methods MTT assay was used to measure the proliferation suppression of MCF-7 cells after treated with 1.0, 2.5, 5.0, 10.0, and 20.0 μg/m L TPP for 48 h, and then the cell apoptosis rate and expression rate of NF-κB P65 positive cells were tested by flow cytometry after 20.0 μg/m L TPP treatment for 0, 24, and 48 h. Results MTT assay showed that, after treatment for 48 h, 1.0, 2.5, 5.0, 10.0, and 20.0 μg/m L TPP all exhibited the inhibitory effects and showed a dose-dependent relationship. Flow cytometry results showed that 20.0 μg/m L TPP induced cell apoptosis after treatment for 24 and 48 h. TPP（20.0 μg/m L） significantly reduced the rate of NF-κB P65-positive cells in MCF-7 cells after treatment for 48 h. Conclusion TPP could inhibit the proliferation of MCF-7 cells, which may be induced by cell apoptosis. Down-regulation of NF-κB is possible to be related with apoptosis.

关 键 词：毛叶假鹰爪素C 衍生物 MCF-7 凋亡 NF-κB 

分 类 号：R965[医药卫生—药理学]