TIPE3上调P-gp表达降低乳腺癌细胞对阿霉素的敏感性

doi:10.6040/j.issn.1671-7554.0.2017.210

摘要/Abstract

摘要： 目的探讨新的促癌分子肿瘤坏死因子-α诱导蛋白8样蛋白3(TIPE3)是否影响乳腺癌细胞MCF-7对阿霉素的敏感性及其机制。方法以0、0.5、1.0、1.5 μg/mL阿霉素作用于TIPE3表达质粒转染的MCF-7细胞,分别采用细胞活性检测试剂盒(CCK-8)、流式细胞术分析TIPE3对阿霉素作用的MCF-7细胞相对活性及细胞周期分布的影响;采用Annexin V/PI染色流式细胞术检测分析TIPE3对阿霉素作用的MCF-7细胞凋亡的影响;采用实时荧光定量PCR(qRT-PCR)法和蛋白印记(Western blotting)法检测核因子-kappa B(NF-κB)信号通路活化情况、多药耐药基因1(MDR 1)及多药耐药蛋白P-糖蛋白(P-gp)的表达。结果过表达TIPE3增加了阿霉素处理MCF-7细胞的相对存活率和G2/M期细胞数,降低细胞凋亡率;NF-κB信号通路活化水平增加,多药耐药基因MDR1及其表达蛋白P-gp的表达水平升高。结论 TIPE3通过活化NF-κB信号通路上调P-gp的表达进而降低MCF-7细胞对阿霉素的敏感性。

关键词: 乳腺癌, P-糖蛋白, 肿瘤坏死因子-α诱导蛋白8样蛋白3, 核因子-kappa B, 阿霉素

Abstract: Objective To investigate the mechanisms of tumor necrosis factor-α induced protein 8 like 3(TIPE3), a recently investigated oncogenic transfer protein, on modulating breast cancer cell MCF-7 sensitivity to adriamycin. Methods TIPE3-overexpressed MCF-7 cells were treated with 0, 0.5, 1.0, 1.5 μg/mL adriamycin. After that, the relative viability and cell cycle of MCF-7 cells were detected with CCK-8 method and flow cytometry; the apoptosis of MCF-7 cells was assessed with Annexin V/PI; expression of MDR 1/P-gp and activation of NF-κB signal pathway were detected with qRT-PCR and Western blotting. Results Overexpressed TIPE3 promoted MCF-7 cell proliferation, increased the number of G2/M cells and inhibited apoptosis. Furthermore, overexpressed TIPE3 protein upregulated the activation of NF-κB signal pathway and the expression of MDR1/P-gp. Conclusion TIPE3 decreased MCF-7 cells sensitivity to adriamycin by upregulating the expression of P-gp via NF-κB pathway.

Key words: Nuclear factor-kappa B, Adriamycin, Tumor necrosis factor-α induced protein 8 like 3, Breast cancer, P-gp

中图分类号:

R392.11

廉开礼,李炎,张娜,靳桂媛,刘素侠. TIPE3上调P-gp表达降低乳腺癌细胞对阿霉素的敏感性[J]. 山东大学学报（医学版）, 2017, 55(5): 36-42.

LIAN Kaili, LI Yan, ZHANG Na, JIN Guiyuan, LIU Suxia. TIPE3 decreases breast cancer cell sensitivity to adriamycin by upregulating P-gp protein expression[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 36-42.

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