汉黄芩素经PTEN/PI3K/AKT信号通路对乳腺癌细胞增殖的影响  

Effects of baicalein on breast cancer cell proliferation via PTEN/PI3K/AKT signaling pathway

作　　者：陈旭[1] 郑玉 彭泉 陈亮[1] 张明金 赵成功[1] 任桂灵 Chen Xu;Zheng Yu;Peng Quan(Dept of General Surgery,The 901 Hospital of The Joint Logistics Support Force of The Chinese People's Liberation Army,Hefei 230032)

机构地区：[1]中国人民解放军联勤保障部队第九○一医院普外科,合肥230032 [2]中国人民解放军联勤保障部队第九○一医院药剂科,合肥230032

出　　处：《安徽医科大学学报》2021年第3期363-368,共6页Acta Universitatis Medicinalis Anhui

基　　金：安徽省自然科学基金(编号:1908085QH377)。

摘　　要：目的探讨汉黄芩素对乳腺癌细胞mcf-7与裸鼠移植瘤的影响及其可能涉及的分子机制。方法采用CCK-8检测不同浓度(0、20、50、100μmol/L)汉黄芩素对乳腺癌细胞增殖的影响;通过流式细胞术检测汉黄芩素对乳腺癌细胞周期分布和凋亡率的影响;运用转录组测序分析汉黄芩素可能影响的信号通路;运用Western blot检测汉黄芩素对相关蛋白的影响;此外,通过裸鼠移植瘤模型的体内实验探究汉黄芩素对裸鼠移植瘤的影响。结果与对照组相比,汉黄芩素可以通过抑制乳腺癌细胞的增殖能力诱导乳腺癌细胞周期阻滞,并且诱导其凋亡,呈时间和浓度依赖性;同时,汉黄芩素处理mcf-7细胞48 h后,增殖标志性蛋白PCNA的表达水平降低,Cleaved-Caspase3蛋白表达水平逐渐升高,Caspase-3蛋白表达水平逐渐降低;此外,汉黄芩素还可以调节PTEN/PI3K/AKT信号通路,抑癌蛋白PTEN表达水平随着浓度升高逐渐增加,p-PI3K和p-AKT蛋白表达水平随着浓度升高降低;同时,体内实验初步显示汉黄芩素可以抑制mcf-7裸鼠移植瘤的生长。结论汉黄芩素对乳腺癌细胞系mcf-7的增殖具有抑制作用,并且诱导其凋亡,其机制可能与PTEN/PI3K/AKT信号轴的调节有关,为汉黄芩素的抗肿瘤活性提供新的基础。Objective To investigate the effect of baicalein on breast cancer cell mcf-7 and xenograft tumor in nude mice and its possible molecular mechanism.Methods CCK-8 was used to detect the effect of different concentrations(0,20,50,100μmol/L)of baicalein on the proliferation of breast cancer cells;flow cytometry was used to detect the cycle distribution and apoptosis rate of breast cancer cells.Transcriptome sequencing was used to analyze the possible signaling pathways affected by baicalein.Western blot was used to detect the effects of baicalein on related proteins;in addition,in vivo experiments with nude mice xenograft model were used to explore the effects of baicalein on nude mice Impact.Results Compared with the control group,baicalein could inhibit the proliferation of breast cancer cells in a time-and concentration-dependent manner,induce breast cancer cell cycle arrest,and significantly induce its apoptosis;meanwhile,after baicalein treated mcf-7 cells 48 h,the expression level of PCNA,a marker of proliferation,significantly reduced.The expression level of Cleaved-Caspase3 protein gradually increased,and the expression level of Caspase3 protein gradually reduced.In addition,baicalein could also regulate the PTEN/PI3K/AKT signaling pathway.The expression level of tumor suppressor protein PTEN gradually increased with concentration increasing,and the expression levels of p-PI3K and p-AKT protein decreased significantly with concentration increasing;meanwhile,in vivo experiments showed that baicalein could inhibit mcf-7 xenograft tumor growth.Conclusion Baicalein has an inhibitory effect on the proliferation of breast cancer cell line mcf-7 and induces apoptosis.The mechanism may be related to the regulation of PTEN/PI3K/AKT signal axis,providing a new antitumor activity for baicalein basis.

关 键 词：汉黄芩素 乳腺癌 MCF-7 增殖 凋亡 PTEN/PI3K/AKT 裸鼠移植瘤模型 

分 类 号：R737.9[医药卫生—肿瘤]