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TRIM47 抑制顺铂化疗敏感性和内质网应激诱导的卵巢癌细胞凋亡。

TRIM47 inhibits cisplatin chemosensitivity and endoplasmic reticulum stress-induced apoptosis of ovarian cancer cells.

机构信息

Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang, 110042, China.

Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang, 110042, China.

出版信息

Mol Cell Probes. 2024 Oct;77:101978. doi: 10.1016/j.mcp.2024.101978. Epub 2024 Aug 3.

DOI:10.1016/j.mcp.2024.101978
PMID:39096978
Abstract

Ovarian cancer (OC) is the fifth most common cause of death in women worldwide. Chemoresistance is a key reason for treatment failure, causing high mortality. As a member of the tripartite motif-containing (TRIM) protein family, tripartite motif 47 (TRIM47) plays a vital role in the carcinogenesis and drug resistance of various cancers. This study investigated the impact and mechanisms of TRIM47 on cisplatin (DDP) chemosensitivity and apoptosis in OC. OC cell viability was assessed with a cell counting kit-8 assay and OC cell apoptosis was assessed using flow cytometry, caspase-3 and caspase-9 activity, and Bax and Bcl-2 expression assays while gene and protein expression were assessed using qRT-PCR and Western blot assays. The expression of TRIM47 was significantly increased in both DDP-resistant tissues from patients with OC tissues and in cancer cell lines compared with that in normal tissue or parental cell lines. The increased level of TRIM47 correlated with poor prognosis in patients with OC. Functional assays demonstrated that TRIM47 promoted DDP resistance both in vitro and in vivo. The increased viability and reduced apoptosis of OC cells induced by TRIM47 can be rescued by the endoplasmic reticulum (ER) stress-inducer tunicamycin, suggesting that TRIM47 inhibits OC cell apoptosis by suppressing ER stress. Therefore, TRIM47 may be targeted as a therapeutic strategy for DDP resistance in OC.

摘要

卵巢癌(OC)是全球女性第五大常见死因。化疗耐药是治疗失败的一个关键原因,导致高死亡率。作为三肽基结构域(TRIM)蛋白家族的一员,三肽基结构域 47(TRIM47)在各种癌症的发生和耐药中起着至关重要的作用。本研究探讨了 TRIM47 对 OC 顺铂(DDP)化疗敏感性和细胞凋亡的影响及其机制。通过细胞计数试剂盒-8 测定评估 OC 细胞活力,通过流式细胞术、caspase-3 和 caspase-9 活性以及 Bax 和 Bcl-2 表达测定评估 OC 细胞凋亡,同时通过 qRT-PCR 和 Western blot 测定评估基因和蛋白表达。与正常组织或亲本细胞系相比,OC 患者耐药组织和癌细胞系中 TRIM47 的表达均显著增加。TRIM47 水平的升高与 OC 患者的不良预后相关。功能测定表明,TRIM47 无论是在体外还是在体内均促进 DDP 耐药。TRIM47 诱导的 OC 细胞活力增加和凋亡减少可被内质网(ER)应激诱导剂衣霉素挽救,表明 TRIM47 通过抑制 ER 应激抑制 OC 细胞凋亡。因此,TRIM47 可能成为 OC 中 DDP 耐药的治疗策略靶点。

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