甘草查尔酮B对三阴性乳腺癌MDA-MB-231细胞的抑制作用及其机制

The inhibitory effect of Licochalcone B on the triple negative breast cancer cell MDA-MB-231 and its mechanism

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摘要目的:探讨甘草查尔酮B(LCB)对三阴性乳腺癌(TNBC)MDA-MB-231细胞的抑制作用及其机制。方法:常规培养MDA-MB-231细胞,用不同浓度LCB处理后,采用CCK-8法、免疫荧光法、FCM和WB法分别检测MDA-MB-231细胞的增殖活力、细胞核内DNA双链断裂标志物γ-H2AX的表达,以及细胞周期和周期调控、丝裂原活化蛋白激酶(MAPK)、内质网应激信号途径相关蛋白的表达水平。结果:LCB能显著抑制乳腺癌MDA-MB-231细胞的增殖活力(P<0.05),使γ-H2AX阳性细胞数和蛋白表达水平均显著升高(均P<0.05)、G2/M和S期的细胞数量均明显增加(均P<0.05)、MAPK家族主要成员细胞外调节激酶1/2(ERK1/2)和p38MAPK蛋白的磷酸化水平均显著上调(均P<0.05),还使内质网应激途径相关蛋白Bip、ATF4和CHOP的表达均显著上调(均P<0.05)。结论:LCB能够显著抑制MDA-MB-231细胞的增殖活力、诱导DNA损伤和细胞周期阻滞于G2/M和S期,LCB对MDA-MB-231细胞的抑制作用可能与其激活MAPK和内质网应激信号通路相关。 Objective:To investigate the inhibitory effect of Licochalcone B(LCB)on a triple-negative breast cancer cell line MDA-MB-231 cells and its mechanism.Methods:MDA-MB-231 cells were routinely cultured and treated with different concentrations of LCB,and then CCK-8 assay,immunofluorescence,FCM and WB analysis were used to detect the proliferative viability of MDA-MB-231 cells,the expression ofγ-H2AX,a marker of DNA double-strand breaks in the nucleus,the cell cycle,and the expression levels of proteins related to cycle regulation,mitogen-activated protein kinase(MAPK),and the endoplasmic reticulum stress(ER stress),respectively.Results:LCB significantly inhibited the proliferative viability of breast cancer MDA-MB-231 cells(all P<0.05),the number ofγ-H2AX-positive cells and protein expression levels were significantly increased after LCB treatment(all P<0.05),the number of cells in G2/M and S phases was significantly increased(all P<0.05),the phosphorylation levels of the main members of the MAPK family,extracellular regulated kinase 1/2(ERK1/2)and p38 MAPK phosphorylation levels were significantly upregulated(all P<0.05),and the expression of ER stress pathway-related proteins Bip,ATF4 and CHOP were significantly upregulated(all P<0.05).Conclusion:LCB could significantly inhibit the proliferation vitality of MDA-MB-231 cells and induce DNA damage and cell cycle arrest at G2/M and S phases.The inhibitory effect of LCB on MDA-MB-231 cells may be related to the activation of MAPK and ER stress signaling pathway.

作者王琳琳曹露杨洪川王凤泽吴开祥 WANG Linlin;CAO Lu;YANG Hongchuan;WANG Fengze;WU Kaixiang(School of Life Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences,Taian 271000,Shandong,China;Department of Pathology,the Second Affiliated Hospital of Shandong First Medical University,Taian 271000,Shandong,China)

机构地区山东第一医科大学暨山东省医学科学院生命科学学院山东第一医科大学第二附属医院病理科

出处《中国肿瘤生物治疗杂志》 CSCD 北大核心 2023年第12期1061-1065,共5页 Chinese Journal of Cancer Biotherapy

基金山东省自然科学基金(No.ZR2018MH026) 泰安市科技创新发展项目(No.2022NS322,No.2022NS353)。

关键词甘草查尔酮B 三阴性乳腺癌 MDA-MB-231细胞增殖 DNA损伤细胞周期阻滞丝裂原活化蛋白激酶内质网应激 Licochalcone B(LCB) triple-negative breast cancer(TNBC) MDA-MB-231 cell proliferation DNA damage cell cycle arrest mitogen-activated protein kinase(MAPK) endoplasmic reticulum stress(ER stress)