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目的 探讨瑞芬太尼对乳腺癌MDA-MB-231细胞增殖、凋亡及Wnt/β-连环蛋白(β-catenin)通路的影响。方法 用不同浓度瑞芬太尼(0、0.5、2.5、5.0、10.0、20.0、40.0μg/mL)处理人正常乳腺MCF-10A细胞和乳腺癌MDA-MB-231细胞筛选瑞芬太尼的实验浓度。将MDA-MB-231细胞分为对照组、瑞芬太尼低(5.0μg/mL)、中(10.0μg/mL)、高(20.0μg/mL)浓度组、瑞芬太尼+SKL2001(Wnt/β-catenin通路激动剂)组; MTT实验和集落形成实验检测细胞增殖能力;流式细胞术检测细胞凋亡及细胞周期变化; Western blot检测细胞增殖、凋亡和Wnt/β-catenin信号通路相关蛋白表达。结果 5.0、10.0、20.0μg/mL瑞芬太尼可降低MDA-MB-231细胞活力，并对MCF-10A细胞无明显毒性。与对照组相比，瑞芬太尼低、中、高浓度组细胞增殖的光密度值、集落形成数、S期细胞比例、细胞髓细胞瘤病基因(c-Myc)、细胞周期素D1、B淋巴细胞瘤2(Bcl-2)、半胱天冬氨酸蛋白酶3前体(pro-caspase-3)、β-catenin蛋白水平降低(P<0.05),G0/G1期细胞比例、细胞凋亡率、早期凋亡率、Bcl-2相关X蛋白(Bax)和激活型半胱天冬氨酸蛋白酶3(Cleaved caspase-3)、糖原合酶激酶3β(GSK-3β)蛋白水平增加(P<0.05);SKL2001可削弱瑞芬太尼对MDA-MB-231细胞增殖和凋亡的影响。结论 瑞芬太尼可抑制MDA-MB-231细胞增殖，诱导细胞凋亡和细胞周期停滞，其机制可能与抑制Wnt/β-catenin信号通路激活有关。
Abstract：Objective To investigate the impacts of remifentanil on the proliferation,apoptosis and Wnt/β-catenin pathway of breast cancer MDA-MB-231 cells. Methods Different concentrations of remifentanil(0,0. 5,2. 5,5. 0,10. 0,20. 0,40. 0 μg/mL) were used to treat human normal breast MCF-10A cells and breast cancer MDAMB-231 cells to screen for experimental concentrations of remifentanil. MDA-MB-231 cells were divided into control group,remifentanil low(5. 0 μg/mL),medium(10. 0 μg/mL),and high(20. 0 μg/mL) concentration groups,and remifentanil + SKL2001(Wnt/β-catenin pathway agonist) group. MTT assay and colony formation assay were applied to detect cell proliferation ability. Flow cytometry was applied to detect cell apoptosis and cell cycle changes. Western blot was applied to detect protein expression related to cell proliferation,apoptosis,and the Wnt/β-catenin signaling pathway. Results Remifentanil at concentrations of 5. 0,10. 0,and 20. 0 μg/mL could reduce the viability of MDA-MB-231 cells and had no prominent toxicity to MCF-10A cells. Compared with the control group,the optical density value of cell proliferation,colony formation number,proportion of S-phase cells,and the protein levels of cellular myelocytomatosis(c-Myc),Cyclin D1,B lymphoblastoma 2(Bcl-2),precursor of cysteine aspartate protease-3(pro-caspase-3) and β-catenin were lower in the low,medium,and high concentration remifentanil groups(P < 0. 05),while the proportion of G0/G1 phase cells,apoptosis rate,early apoptosis rate,the protein levels of Bcl-2 associated X protein(Bax) and cleaved cysteine aspartate protease-3(Cleaved caspase-3),and glycogen synthase kinase-3β(GSK-3β) were higher(P < 0. 05). SKL2001 could weaken the effects of remifentanil on the proliferation and apoptosis of MDA-MB-231 cells. Conclusion Remifentanil inhibits the proliferation of MDA-MB-231 cells,induces apoptosis and cell cycle arrest,and its mechanism may be related to the inhibition of Wnt/β-catenin signaling pathway activation.
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基本信息:
DOI：10.19405/j.cnki.issn1000-1492.2025.09.006
中图分类号:R614;R737.9
引用信息:
[1]张杨,刘文文,苗欢欢,等.瑞芬太尼对乳腺癌MDA-MB-231细胞增殖、凋亡及Wnt/β-catenin通路的影响[J].安徽医科大学学报,2025,60(09):1606-1613.DOI:10.19405/j.cnki.issn1000-1492.2025.09.006.
基金信息:
河北省医学科学研究课题计划项目(编号：20231512)~~