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冬凌草甲素逆转乳腺癌MCF-7细胞对氟维司群耐药的机制研究 Δ

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胡高波 ，朱 瑞 ，金 湛 ，魏自太 （1.衢州职业技术学院医学院，浙江 衢州 324000；2.浙江中医药大学药学
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院，杭州 310053）
中图分类号 R965；R737.9 文献标志码 A 文章编号 1001-0408（2022）17-2119-05
DOI 10.6039/j.issn.1001-0408.2022.17.14

摘 要 目的 探究冬凌草甲素（Ori）逆转乳腺癌MCF-7细胞对氟维司群（Ful）耐药的机制。方法 在体外诱导构建乳腺癌获得性
Ful耐药细胞株MCF-7/Ful；采用MTT法检测MCF-7细胞和MCF-7/Ful细胞的相对细胞活力，Ori对MCF-7/Ful细胞的抑制率；采
用CompuSyn软件分析Ori和Ful的协同效应；将MCF-7/Ful细胞随机分为空白对照组、Ful组（5 μmol/L）、Ori组（8 μmol/L）、Ful（5
μmol/L）+Ori（8 μmol/L）组，采用Western blot法检测各组细胞中磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（Akt）信号通路相关蛋白的
磷酸化情况。采用MCF-7/Ful细胞制备裸鼠移植瘤耐药模型，随机分为空白对照组、Ful组（80 μmol/g）、Ori组（50 μmol/g）、Ful（80
μmol/g）+Ori（50 μmol/g）组，计算肿瘤质量和抑瘤率，验证 Ori 在体内的耐药逆转作用。结果 MTT 法检测结果显示，当 Ful≥10
μmol/L时，MCF-7/Ful细胞的相对细胞活力显著高于MCF-7细胞（P＜0.05），耐药性显著增强；Ori对MCF-7/Ful细胞具有明显的抑
制作用，与Ful联合使用对MCF-7/Ful细胞的抑制率显著升高（P＜0.05或P＜0.01），逆转耐药效果显著增加。Western blot法检测
结果显示，与Ful组比较，Ful+Ori组细胞中PI3K、Akt磷酸化水平均显著降低（P＜0.05或P＜0.01）。体内实验结果显示，Ful+Ori
组裸鼠的肿瘤体积和质量显著下降，抑瘤率为（63.90±4.11）％，较Ful组显著升高（P＜0.01）。结论 Ori可以逆转乳腺癌MCF-7细
胞对Ful的耐药性，此作用可能是通过调控PI3K/Akt信号通路实现的。
关键词 冬凌草甲素；氟维司群；磷脂酰肌醇-3-激酶/蛋白激酶B信号通路；乳腺癌；耐药逆转

Study on the mechanism of oridonin to reverse drug resistance of breast cancer cell MCF-7 to fulvestrant
HU Gaobo ，ZHU Rui ，JIN Zhan ，WEI Zitai（1. Medical School，Quzhou College of Technology，Zhejiang
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Quzhou 324000，China；2. College of Pharmacy，Zhejiang Chinese Medical University，Hangzhou 310053，
China）
ABSTRACT OBJECTIVE To explore the mechanism of oridonin （Ori） reversing the drug resistance of breast cancer cell
MCF-7 to fulvestrant（Ful）. METHODS Ful-resistant breast cancer cell strains MCF-7/Ful were induced and constructed in vitro.
The relative cell viability of MCF-7 cells and MCF-7/Ful cells was detected by MTT assay，inhibitory rate of Ori to MCF-7/Ful
cells was also detected. CompuSyn software was used to analyze the synergistic effect of Ori and Ful. MCF-7/Ful cells were
randomly divided into blank control group，Ful group（5 μmol/L），Ori group（8 μmol/L），Ful（5 μmol/L）+Ori（8 μmol/L）group.
The phosphorylation of phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） signaling pathway related protein in each
group was detected by Western blot. MCF-7/Ful cells were used to prepare drug resistance model of transplanted tumor in nude
mice，and they were randomly divided into blank control group，Ful group（80 μmol/g），Ori group（50 μmol/g），Ful（80 μmol/g）+
Ori（50 μmol/g）group. The tumor weight and tumor inhibition rate were calculated，to verify the reversal effect of Ori and Ful in
vivo. RESULTS MTT assay showed that when Ful≥10 μmol/L，the relative cell viability of MCF-7/Ful cells was significantly
higher than that of MCF-7 cells（P＜0.05），and the drug resistance was significantly enhanced；Ori had a significant inhibitory
effect on MCF-7/Ful cells，the inhibition rate of Ori combined with Ful to MCF-7/Ful cells was significantly increased（P＜0.05 or
P＜0.01），and the effect of reversing drug resistance was significantly increased. The results of Western blot showed that compared
with Ful group，the phosphorylation levels of PI3K and Akt protein in Ful+Ori group were significantly decreased（P＜0.05 or P＜
0.01）. In vivo results showed that the tumor volume and mass of Ful + Ori group were significantly decreased，and the tumor
inhibition rate was（63.90±4.11）％，which was significantly higher than that of Ful group（P＜0.01）. CONCLUSIONS Ori can
reverse drug resistance of breast cancer cell MCF-7 to Ful，
Δ 基金项目 衢州市科技计划项目（No.2019K41）；衢州市重点创 and this effect may be through regulating PI3K/Akt signaling
新团队资助项目（No.衢委人才〔2017〕6号）
pathway.
＊第一作者 讲师，硕士。研究方向：抗肿瘤药物活性。电话：
KEYWORDS oridonin；fulvestrant；phosphatidylinositol 3
0570-8068091。E-mail：740328775@qq.com
kinase/protein kinase B signaling pathway； breast cancer；
# 通信作者 教授，博士。研究方向：中医药抗肿瘤。电话：0570-
8068091。E-mail：wztyang@163.com reversal of drug resistance

中国药房 2022年第33卷第17期 China Pharmacy 2022 Vol. 33 No. 17 ·2119 ·