Institute of Precision Medicine, Jining Medical University, 272067, Jining, China.
Center for Experimental Medicine, School of Public Health, Jining Medical University, 272067, Jining, China.
Cell Death Dis. 2022 Dec 12;13(12):1034. doi: 10.1038/s41419-022-05490-5.
Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.
尽管第二代疗法如阿比特龙（ABI）和恩扎鲁胺（ENZ）有益于去势抵抗性前列腺癌（CRPC）患者，但药物耐药性经常发生，最终导致治疗失败。在这项研究中，我们使用了两个文库，即 FDA 批准药物文库和 CRISPR/Cas9 基因敲除（GeCKO）文库，以筛选克服治疗耐药性的药物，并鉴定涉及治疗耐药性的潜在耐药基因。我们的筛选结果表明，DNA 损伤剂伊达比星（IDA）可克服前列腺癌细胞对阿比特龙和恩扎鲁胺的耐药性。IDA 治疗以转录非依赖性方式抑制 DNA 修复蛋白 XPA 的表达。一致地，XPA 基因敲除使前列腺癌细胞对阿比特龙和恩扎鲁胺的治疗更敏感。总之，IDA 通过降低前列腺癌细胞中的 XPA 蛋白水平来对抗阿比特龙和恩扎鲁胺的耐药性。
Zotero 插件
