文献类型：期刊文献

中文题名：冬凌草甲素通过CDC42/MAP3K10通路抑制人乳腺癌MDA-MB-231细胞增殖、迁移和侵袭的研究

英文题名：Oridonin Inhibits the Proliferation,Migration,and Invasion of MDA-MB-231 Breast Cancer Cells via CDC42/MAP3K10 Signaling Pathway

作者：李志明[1];龙凤[1,2];黄勇[1];孙少康[1];刘晓燕[1];赵玉[1]

第一作者：李志明

机构：[1]甘肃中医药大学,兰州730000;[2]甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室,兰州730000

第一机构：甘肃中医药大学

年份：2021

卷号：37

期号：6

起止页码：37

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：甘肃省高等学校创新基金项目(编号:2021A-078);甘肃省自然科学基金项目(编号:148RJZA070);甘肃中医药大学中西医结合基础学科科研培育项目(编号:2020-2021)

语种：中文

中文关键词：乳腺癌;冬凌草甲素;迁移;侵袭;丝裂原活化蛋白激酶通路

外文关键词：breast cancer;oridonin;migration;invasion;MAPK signaling pathway

摘要：目的:观察冬凌草甲素对人乳腺癌MDA-MB-231细胞增殖、迁移和侵袭的影响,探究冬凌草甲素抑制人乳腺癌MDA-MB-231细胞分子机制。方法:采用CCK-8法检测冬凌草甲素对乳腺癌MDA-MB-231细胞增殖活力的影响;平板克隆试验分析经冬凌草甲素处理的MDA-MB-231细胞克隆形成能力;细胞划痕试验研究冬凌草甲素对MDA-MB-231细胞迁移能力的影响;Transwell侵袭试验检测冬凌草甲素对MDA-MB-231细胞侵袭能力的抑制作用;免疫印迹法(Western blot)分析检测上皮间质转化(epithelial-mesenchymal transition,EMT)相关标志蛋白Vimentin、E-cadherin、N-cadherin以及MAPK信号通路中的关键蛋白CDC42、MAP3K10的表达。结果:与空白对照组相比,浓度在4μg/mL以上的冬凌草甲素对乳腺癌MDA-MB-231细胞活力具有显著抑制作用(P<0.01);冬凌草甲素2、4、6μg/mL均能降低乳腺癌MDA-MB-231细胞的克隆形成能力、迁移和侵袭能力,上调E-cadherin蛋白的表达、下调Vimentin、N-cadherin的蛋白表达,同时,也可抑制MAPK信号通路中关键蛋白CDC42、MAP3K10的表达(P<0.05或P<0.01)。结论:冬凌草甲素对人乳腺癌MDA-MB-231细胞增殖、迁移和侵袭具有抑制作用,这种抑制作用的分子机制可能是通过影响细胞的EMT进程以及抑制MAPK信号通路中关键蛋白CDC42、MAP3K10的表达来实现的。
Objective:To observe the effects and molecular mechanism of oridonin on the proliferation,migration,and invasion of human breast cancer MDA-MB-231 cells.Methods:The effect of oridonin on the viability of MDA-MB-231 cells was detected by CCK-8 assay.Colony formation assay was used to analyze the cloning ability of MDA-MB-231 cells treated with oridonin.Wound healing assay was used to observe the effect of oridonin on the migration of MDA-MB-231 cells.Transwell invasion assay was used to detect the inhibitory effect of oridonin on the invasion of MDA-MB-231 cells.Western blot was used to detect the protein expression of vimentin,E-cadherin,N-cadherin related to the epithelial-mesenchymal transition(EMT),and the key proteins CDC42 and MAP3 K10 in the MAPK signaling pathway.Results:Compared with the conditions in the blank control group,oridonin at a concentration of more than 4μg/mL significantly inhibited the viability of MDA-MB-231 cells(P<0.01).Oridonin at 2,4,and 6μg/mL significantly decreased the cloning ability,the migration,and invasion of MDA-MB-231 cells(P<0.05),up regulated E-cadherin expression level,down-regulated the expression levels of vimentin and N-cadherin,and inhibited the expression of key proteins CDC42 and MAP3 K10 in the MAPK signaling pathway(P<0.05 or P<0.01).Conclusion:Oridonin can inhibit the proliferation,migration,and invasion of human breast cancer MDA-MB-231 cells and its mechanism may be achieved by affecting the EMT process of cells and inhibiting the expression of key proteins CDC42 and MAP3 K10 in the MAPK signaling pathway.