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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
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| 篇名： | 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 |
| TITLE： | Study on the mechanism of oridonin to reverse drug resistance of breast cancer cell MCF- 7 to fulvestrant |
| 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（5μmol/L）、Ori组（8μmol/L）、Ful（5μmol/L）+Ori（8μmol/L）组，采用Westernblot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（80μmol/g）、Ori组（50μmol/g）、Ful（80μmol/g）+Ori（50μmol/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≥10μmol/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。Westernblot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。 |
| ABSTRACT： | OBJECTIVE To explore the mechanism of oridon in（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 PI 3K 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 ， and this effect may be through regulating PI 3K/Akt signaling pathway. |
| 期刊： | 2022年第33卷第17期 |
| 作者： | 胡高波，朱瑞，金湛，魏自太 |
| AUTHORS： | HU Gaobo ，ZHU Rui，JIN Zhan，WEI Zitai |
| 关键字： | 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 |
| KEYWORDS： | oridonin；fulvestrant；phosphatidylinositol 3 |
| 阅读数： | 154 次 |
| 本月下载数： | 2 次 |
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