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PSMA5 促进前列腺癌的肿瘤发生过程,并与硼替佐米耐药相关。

PSMA5 promotes the tumorigenic process of prostate cancer and is related to bortezomib resistance.

机构信息

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin.

Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, China.

出版信息

Anticancer Drugs. 2019 Aug;30(7):e0773. doi: 10.1097/CAD.0000000000000773.

Abstract

Proteasome α5 subunit (PSMA5) is related to poor prognosis in various cancers. The first therapeutic proteasome inhibitor, bortezomib, induces apoptosis, suppressing cell growth in many tumor types. However, the effects of PSMA5 and bortezomib in prostate cancer (PCa) are still unknown. In this study, we investigated whether PSMA5 is associated with the tumorigenic progression and the interaction of PSMA5 with bortezomib in PCa. We knocked down PSMA5 with siRNA and studied the changes in cell viability and motility with Cell Counting Kit-8, quantitative PCR, fluorescence-activated cell sorting, scratch, and invasion assays. We also investigated the effect of PSMA5 in PCa cells treated with bortezomib and in those that are resistant to bortezomib. We found that silencing PSMA5 inhibited cell proliferation, induced apoptosis, restricted cell migration and invasion, and demonstrated a coordinated effect with bortezomib. Cells resistant to bortezomib gained sensitivity to bortezomib after PSMA5 was knocked down. Our results show, for the first time, that PSMA5 promotes the tumorigenic process of PCa and is linked to bortezomib resistance.

摘要

蛋白酶体 α5 亚基(PSMA5)与各种癌症的不良预后有关。第一个治疗性蛋白酶体抑制剂硼替佐米诱导细胞凋亡,抑制多种肿瘤类型的细胞生长。然而,PSMA5 和硼替佐米在前列腺癌(PCa)中的作用仍不清楚。在这项研究中,我们研究了 PSMA5 是否与肿瘤发生进展以及 PSMA5 与硼替佐米在 PCa 中的相互作用有关。我们用 siRNA 敲低 PSMA5,并用细胞计数试剂盒-8、定量 PCR、荧光激活细胞分选、划痕和侵袭试验研究细胞活力和迁移的变化。我们还研究了 PSMA5 在硼替佐米处理的 PCa 细胞和对硼替佐米耐药的 PCa 细胞中的作用。我们发现,沉默 PSMA5 抑制细胞增殖,诱导细胞凋亡,限制细胞迁移和侵袭,并与硼替佐米表现出协同作用。敲低 PSMA5 后,对硼替佐米耐药的细胞对硼替佐米的敏感性增加。我们的研究结果首次表明,PSMA5 促进了 PCa 的肿瘤发生过程,并与硼替佐米耐药有关。

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