Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
J Immunol Res. 2022 Jul 21;2022:4065580. doi: 10.1155/2022/4065580. eCollection 2022.
This project attempts to clarify the expression of MUS81 in castration-resistant prostate cancer (CRPC) and the effect on drug sensitivity to Olaparib. We collected clinical surgical samples of patients who were suffering from benign prostatic hyperplasia (BPH), common prostate cancer (PCa), and castration-resistant prostate cancer (CRPC) and detected the expression of MUS81 in healthy prostate epithelial cells, PCa cells, and androgen-independent PCa cells. We subsequently performed CCK-8 assays, flow cytometry, and Transwell invasion and migration assay to determine the proliferation, apoptosis, invasion, and metastasis abilities of transfected CRPC cells as well as drug toxicity of Olaparib to CRPC cells. The expression of MUS81 indicated marked upregulation in PCa and CRPC tissues, compared with the level of MUS81 in BPH tissues. MUS81 silencing inhibited the proliferation of CRPC cells and promoted their sensitivity to Olaparib. MUS81 silencing in CRPC cells remarkably accelerated cell apoptosis and greatly inhibited cell invasion and metastasis after Olaparib administration. MUS81 silencing in CRPC cells has significantly enhanced the sensitivity of cells to Olaparib, which provides evidence for the prediction of Olaparib resistance in CRPC cells by the MUS81 gene and is expected to become a promising gene target in CRPC therapy.
本研究旨在阐明 MUS81 在去势抵抗性前列腺癌（CRPC）中的表达情况及其对奥拉帕利药物敏感性的影响。我们收集了患有良性前列腺增生（BPH）、常见前列腺癌（PCa）和去势抵抗性前列腺癌（CRPC）患者的临床手术样本，并检测了健康前列腺上皮细胞、PCa 细胞和雄激素非依赖性 PCa 细胞中 MUS81 的表达情况。随后，我们通过 CCK-8 检测、流式细胞术和 Transwell 侵袭和迁移实验，确定转染后的 CRPC 细胞的增殖、凋亡、侵袭和转移能力，以及奥拉帕利对 CRPC 细胞的药物毒性。与 BPH 组织中的 MUS81 水平相比，MUS81 在 PCa 和 CRPC 组织中的表达明显上调。沉默 MUS81 抑制了 CRPC 细胞的增殖，并增强了其对奥拉帕利的敏感性。沉默 MUS81 后，CRPC 细胞对奥拉帕利的敏感性明显增强，细胞凋亡显著加快，侵袭和转移受到极大抑制。沉默 MUS81 增强了 CRPC 细胞对奥拉帕利的敏感性，为通过 MUS81 基因预测 CRPC 细胞对奥拉帕利的耐药性提供了依据，有望成为 CRPC 治疗的有前途的基因靶点。
