与卵巢癌细胞系中拓扑替康耐药性发展相关的新基因和旧基因
New and Old Genes Associated with Topotecan Resistance Development in Ovarian Cancer Cell Lines.
作者信息
Klejewski Andrzej, Świerczewska Monika, Zaorska Katarzyna, Brązert Maciej, Nowicki Michał, Zabel Maciej, Januchowski Radosław
机构信息
Department of Nursing, Poznan University of Medical Sciences, Poznan, Poland
Department of Obstetrics and Womens Dieseases, Poznan University of Medical Sciences, Poznan, Poland.
出版信息
Anticancer Res. 2017 Apr;37(4):1625-1636. doi: 10.21873/anticanres.11493.
BACKGROUND
Low effectiveness of chemotherapy in ovarian cancer results from development of drug resistance. Topotecan is a drug used as second-line chemotherapy for this cancer type. We analyzed development of topotecan resistance in ovarian cancer cell lines.
MATERIALS AND METHODS
A chemosensitivity assay, MTT test, was performed to assess drug resistance. Quantitative polymerase chain reaction (Q-PCR) assays were performed to determine ABCB1, ABCG2, ALDH1A1, IFIH1, SAMD4 and EPHA3 gene expression.
RESULTS
We observed dose-dependent responses to topotecan. In all topotecan-resistant cell lines an overexpression of ABCG2, IFIH1 and SAMD4 genes was observed. Expression of ABCB1 gene was observed in one cell line. Expression of ALDH1A1 was up-regulated in A2780 and down-regulated in SKOV-3-resistant cell lines. Short-time exposure led to similar patterns of gene expression for the investigated genes.
CONCLUSION
Expression of ABCG2 and ABCB1 genes plays the most important role in topotecan resistance. The role of other investigated genes seems to be complementary.
背景
卵巢癌化疗效果不佳是由于耐药性的产生。拓扑替康是用于这种癌症二线化疗的药物。我们分析了卵巢癌细胞系中拓扑替康耐药性的产生情况。
材料与方法
进行化学敏感性测定即MTT试验以评估耐药性。进行定量聚合酶链反应（Q-PCR）测定以确定ABCB1、ABCG2、ALDH1A1、IFI1H1、SAMD4和EPHA3基因的表达。
结果
我们观察到对拓扑替康的剂量依赖性反应。在所有拓扑替康耐药细胞系中均观察到ABCG2、IFI1H1和SAMD4基因的过表达。在一个细胞系中观察到ABCB1基因的表达。ALDH1A1的表达在A2780细胞系中上调，而在SKOV-3耐药细胞系中下调。短时间暴露导致所研究基因的基因表达模式相似。
结论
ABCG2和ABCB1基因的表达在拓扑替康耐药中起最重要作用。其他所研究基因的作用似乎具有互补性。
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