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粒细胞巨噬细胞集落刺激因子在乳腺癌细胞中的过表达导致药物敏感性增加。

Overexpression of granulocyte macrophage colony stimulating factor in breast cancer cells leads towards drug sensitization.

作者信息

Chaubey Nidhi, Ghosh Siddhartha Sankar

机构信息

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-39, Assam, India.

出版信息

Appl Biochem Biotechnol. 2015 Feb;175(4):1948-59. doi: 10.1007/s12010-014-1373-5. Epub 2014 Nov 29.

Abstract

This report describes the effect of overexpressing granulocyte macrophage colony stimulating factor (GMCSF) in breast cancer cells, which otherwise is involved in proliferation and differentiation of granulocyte and macrophage lineages. The purified recombinant GMCSF cytokine is known to exert dose-dependent proliferative response on various cancer cells, but its effect during overexpression is yet to be evaluated. In our present study, we have generated MCF-7 (breast cancer) cells overexpressing GMCSF. Interestingly, cell viability studies showed pronounced sensitivity of GMCSF overexpressing MCF-7 cells towards anticancer drugs, such as, doxorubicin, 5FU and cisplatin. These findings were substantiated by cell cycle analysis of the drug-treated GMCSF overexpressing MCF-7 cells. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) results revealed differential expressions of cyclins, and the carboxyfluorescein succinimidyl ester (CFSE)-based assay established decrease in doubling time of GMCSF overexpressed cells with respect to the control populations. Thus, overexpressing of proliferative GMCSF cytokine in breast cancer cells may increase susceptibility to anticancer drugs.

摘要

本报告描述了在乳腺癌细胞中过表达粒细胞巨噬细胞集落刺激因子(GMCSF)的效果,GMCSF原本参与粒细胞和巨噬细胞系的增殖与分化。已知纯化的重组GMCSF细胞因子对各种癌细胞具有剂量依赖性增殖反应,但其在过表达过程中的作用尚未得到评估。在我们目前的研究中,我们构建了过表达GMCSF的MCF-7(乳腺癌)细胞。有趣的是,细胞活力研究表明,过表达GMCSF的MCF-7细胞对阿霉素、5-氟尿嘧啶和顺铂等抗癌药物具有明显的敏感性。对经药物处理的过表达GMCSF的MCF-7细胞进行细胞周期分析,证实了这些发现。半定量逆转录聚合酶链反应(RT-PCR)结果显示细胞周期蛋白表达存在差异,基于羧基荧光素琥珀酰亚胺酯(CFSE)的检测确定过表达GMCSF的细胞相对于对照群体的倍增时间缩短。因此,在乳腺癌细胞中过表达增殖性GMCSF细胞因子可能会增加对抗癌药物的敏感性。

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