PI3k/Akt通路在大戟大枣汤抗不同分子表型乳腺癌中的调控作用
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1.齐齐哈尔医学院;2.齐齐哈尔医学院附属第五医院

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国家自然科学基金项目(82174207);齐齐哈尔市科技局联合引导项目(LHYD-202028);黑龙江省中医药管理局科技计划项目(ZHY2020-179)


Effects of decoction of Euphorbia fischeriana Steud. and jujuba against breast cancer of different molecular phenotypes via PI3k/Akt pathway
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1.Qiqihaer Medical University;2.The fifth affiliated hospital of Qiqihaer Medical University

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    摘要:

    目的 探讨PI3k/Akt通路在大戟大枣汤(decoction of Euphorbia fischeriana Steud. and jujuba,DEFSJ)抗雌激素受体(ER)阴性(-)和ER阳性( )乳腺癌中的调控作用,为乳腺癌的针对性治疗提供参考。方法: 制备DEFSJ提取液,采用UHPLC-Triple Quad仪进行质控分析。采用血清药理学方法制备DEFSJ含药血清(containing serum,CS),乳腺癌(ER-)MDA-MB-453和(ER )MCF-7细胞分别用不同浓度DEFSJ-CS干预48 h。流式细胞术检测细胞周期分布,DNA ladder实验评估细胞凋亡程度,Western blot法检测PI3k/Akt通路相关蛋白表达,实时定量聚合酶链反应(qrt-PCR)法检测FoxO3a、FoxO1a及Bim mRNA表达;激光共聚焦显微镜观察FoxO3a蛋白核转位。结果: UPLC对5批DEFSJ提取物进行了分析,结果表明制备工艺可行,质量可控,保证了药理学实验结果的准确性。体外实验中发现,DEFSJ-CS能阻断细胞在G2/M期(P<0.05,P<0.01);DNA ladder实验中呈现典型的细胞凋亡梯带;与阴性对照组比较,DEFSJ-CS能使p-PI3k、p-Akt、p-FoxO3a及p-FoxO1a蛋白表达降低(P<0.05,P<0.01),Bim蛋白表达升高(P<0.05,P<0.01);使FoxO3a、FoxO1a mRNA表达降低(P<0.05,P<0.01),Bim mRNA表达升高(P<0.05,P<0.01);并能使细胞中FoxO3a蛋白呈现显著的核转位变化;且各数据结果均显示DEFSJ-CS对(ER-)MDA-MB-453细胞比对(ER )MCF-7细胞作用效果更好。结论: PI3k/Akt通路参与了大戟大枣汤抗乳腺癌作用的调控,作用效果因乳腺癌表型差异而不同。

    Abstract:

    Objective To explore the effect of decoction of Euphorbia fischeriana Steud. and jujuba (DEFSJ) against estrogen receptor (ER) negative (-) and ER positive (+) of breast cancer via PI3k/Akt pathway, and to provide reference for targeted treatment of breast cancer. Methods DEFSJ extract was prepared and analysed by using UHPLC-Triple Quad. DEFSJ containing serum (CS) was prepared by a method of serumal pharmacology. Different concentrations of DEFSJ-CS were applied to (ER-) MDA-MB-453 cells and (ER ) MCF-7 of breast cancer in vitro for 48 h. Flow cytometry was used to detect the distribution of cellular cycle,DNA ladder assay was used to assess the degree of apoptosis,and Western blot was used to detect the expression of PI3k/Akt pathway-related proteins. The expressions of FoxO3a, FoxO1a and Bim mRNA were detected by a real-time quantitative polymerase chain reaction (qrt-PCR) method. Nuclear translocation of FoxO3a protein was detected by a confocal laser microscopy. Results Five batches of the DEFSJ extract were analysed by using UPLC, and the results showed that the preparation technology was feasible and the quality was controllable, ensuring the accuracy of pharmacological experiments results. DEFSJ-CS can block cells in G2/M phase (P<0.05,P<0.01). The cells treated with DEFSJ-CS emerged the typical apoptotic ladder in DNA ladder experiment. Compared with negative control group, DEFSJ-CS can decrease the proteins expression of p-PI3k,p-Akt,p-FoxO3a and p-FoxO1a (P<0.05, P<0.01) and can increase the proteins expression of Bim (P<0.05, P<0.01), and can decrease the mRNAs expression of FoxO3a and FoxO1a (P<0.05, P<0.01) and can increase the mRNA expression of Bim (P<0.05, P<0.01), and can enhance nuclear translocation of FoxO3a protein in the cells. Besides, these datas all showed that DEFSJ-CS had better effect on (ER-) MDA-MB-453 cells than (ER ) MCF-7 cells. Conclusion The regulatory effect of the DEFSJ extract on anti-breast cancer is involves the PI3k/Akt pathway, and the effect is varies with phenotypic differences.

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  • 收稿日期:2023-04-19
  • 最后修改日期:2023-05-12
  • 录用日期:2024-02-26
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