饮酒通过内质网应激促进小鼠乳腺癌恶性进展
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国家自然科学基金(No.30973424,No.81272258)。


Ethanol promotes the progression of breast cancer in mice by activating endoplasmic reticulum stress
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    摘要:

    目的 通过动物实验及体外实验探索饮酒是否促进乳腺癌恶性进展,且这一作用是否与其诱导的慢性应激有关。方法 利用小鼠乳腺癌移植瘤模型,体内观察2%乙醇慢性处理的小鼠乳腺癌E0771细胞对体内细胞生长转移的影响;利用体外细胞学实验观察0.2%乙醇慢性诱导对小鼠乳腺癌细胞E0771增殖、迁移及非锚定生长能力的影响;同时用分子生物学方法探索细胞内ROS水平及慢性内质网应激蛋白如p-eIF2a、Bip、XBP1-s等蛋白表达水平是否发生改变。结果 与对照组相比,饮酒组小鼠体内肿瘤生长速度加快,转移增加;体外酒精处理可以显著促进乳腺癌细胞增殖、迁移等恶性生物学行为,酒精慢性处理可以诱导ROS、内质网应激活化蛋白p-eIF2a、Bip、XBP1-s表达上升。结论 饮酒可能通过诱导乳腺癌细胞内质网应激促进其恶性进展。

    Abstract:

    Objective Epidemiological studies have suggested that alcohol drinking is closely associated with diverse tumor development,but fewer laboratory studies or mechanism analysis is made.Our study aims to explore the effect of alcohol on the tumorigenicity and metastasis of breast cancer in nude mice in vivo and on the malignant behavior in vitro, and whether it is related to endoplasmic reticulum stress (ERS).Methods We first established the nude mouse model of breast cancer with chronic alcohol consumption (2%) and to detect the effects of ethanol on tumor growth and metastasis.We also observed the changes of malignant biological behavior of EO771 cells in cell culture induced by chronic alcohol treatment (0.2%) using MTT,Transwell and soft agar tests,and detect the expression of ROS and ERS marker,i.e.p-eIF2a,Bip,and XBP1-s.Results The in vivo experiment showed that alcohol drinking enhanced the growth and metastases of breast cancer in nude mice.The in vitro test showed that chronic exposure to ethanol also promoted the cell proliferation and migration ability,increased the ROS expression,activated ERS pathway,and enhanced the expression of p-eIF2a,Bip and XBP1-s.Conclusions Alcohol drinking may promote the malignant behavior of breast cancer cells through endoplasmic reticulum stress.

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朱佩,刘亚坤,姜玉,汪思应.饮酒通过内质网应激促进小鼠乳腺癌恶性进展[J].中国实验动物学报,2017,25(6):605~610,617.

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  • 收稿日期:2017-03-03
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  • 在线发布日期: 2017-12-16
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