Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Anticancer Agents Med Chem. 2020;20(12):1487-1496. doi: 10.2174/1871520620666200424130934.
Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor.
In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance.
Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined.
The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells.
These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.
顺铂是癌症化疗中一种重要的抗癌药物，但当耐药细胞出现时，治疗变得困难，预后较差。
本研究旨在探讨顺铂敏感和耐药细胞中的基因表达谱，并鉴定与顺铂耐药相关的基因。
比较基因表达谱显示，UBE2L6 mRNA 在耐药细胞中高表达。为了阐明 UBE2L6 是否参与获得顺铂耐药性，我们从顺铂敏感细胞中建立了 UBE2L6 过表达细胞，从顺铂耐药细胞中建立了 UBE2L6 沉默细胞，并检测了顺铂的敏感性。
与对照细胞相比，UBE2L6 过表达细胞的敏感性没有改变，但 UBE2L6 沉默细胞对顺铂敏感。为了阐明 UBE2L6 在顺铂耐药中的机制，我们比较了 UBE2L6 沉默细胞和对照细胞的基因表达谱，发现涉及顺铂耐药的 ABCB6 mRNA 水平降低。此外，UBE2L6 沉默细胞中 ABCB6 启动子活性部分受到抑制。
这些结果表明，顺铂耐药细胞上调了 UBE2L6 的表达，并通过调节 ABCB6 的表达在转录水平上促进顺铂耐药。UBE2L6 可能是克服顺铂耐药性的分子靶点。
