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FANCF在三阴性乳腺癌细胞紫杉醇耐药中的作用及其机制

马芸 柴文英 李姝墨 董坚

中国肿瘤生物治疗杂志2018,Vol.25Issue(3):240-245,6.
中国肿瘤生物治疗杂志2018,Vol.25Issue(3):240-245,6.DOI:10.3872/j.issn.1007-385x.2018.03.005

FANCF在三阴性乳腺癌细胞紫杉醇耐药中的作用及其机制

The effects of FANCF on paclitaxel-resistant triple negative breast cancer cell

马芸 1柴文英 2李姝墨 2董坚2

作者信息

  • 1. 昆明医科大学,云南昆明650500
  • 2. 昆明医科大学第一附属医院乳腺外科,云南昆明650032
  • 折叠

摘要

Abstract

Objective:To establish paclitaxel(PTX)-resistant human triple negative breast cancer cell line and to examine the expression profile of FA-related genes and FANCF,the correlation between the expression of FA-related genes,FANCF and PTX-resistance in breast cancer were further analyzed.Methods:PTX-resistant MDA-MB-231 cell line was established by means of long-term PTX-exposed culture.The sensitivity of the cells to paclitaxel was determined by the CCK8 assay.The cell cycle distribution was examined by flow cytometry after exposure to the paclitaxel.The expression of FA-related gene mRNA and FANCF protein were examined by using real time quantitative PCR and Western blotting.The expression of FANCF in the cells was reduced by RNAi interference technology and the effect of the RNAi was verified.Results:MDA-MB-231/PTX cell showed a 9.9-fold resistance to paclitaxel,indicating that the cell had acquired resistance to PTX.PTX treatment significantly induced G0/G1 arrest and the number of cells in phase S markedly decreased after exposure to PTX.The mRNA and protein expression of FANCF was significantly higher in PTX-resistant cell than that in PTX-sensitve parental cell,Knockdown of FANCF induced apoptosis in MDA-MB-231/PTX cell as well as in parental cell.FANCF knockdown increased the sensitivity of paclitaxel to both MDA-MB-231 and MDA-MB-231/PTX cells (P<0.05 or P<0.01).Conclusion:FANCFplayed an important role in PTX resistance of the breast cancer cells and FANCF might be a target for therapy aimed at reversing chemoresistance.

关键词

乳腺癌/MDA-MB-231细胞/紫杉醇/耐药/FA/BRCA相关基因/FANCF基因

Key words

breast cancer/MDA-MB-231 cell/paclitaxel/chemoresistance/FA/BRCA related genes/FANCF gene

分类

医药卫生

引用本文复制引用

马芸,柴文英,李姝墨,董坚..FANCF在三阴性乳腺癌细胞紫杉醇耐药中的作用及其机制[J].中国肿瘤生物治疗杂志,2018,25(3):240-245,6.

基金项目

国家自然科学基金项目(No.81660472) (No.81660472)

云南省卫生系统领军人才培养计划(No.L-201212) (No.L-201212)

云南省细胞治疗技术转化医学重点实验室基金(No.2015DG034).Project supported by the National Natural Science Foundation of China (No.81660472),the Yunnan Health System Leader Training Program (No.L-201212),and the Key Medical Laboratory Fund of Cell Therapy Technology Transfer of Yunnan Province(No.2015DG034) (No.2015DG034)

中国肿瘤生物治疗杂志

OA北大核心CSCDCSTPCD

1007-385X

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