TRIM47 可抑制顺铂化学敏感性和内质网应激诱导的卵巢癌细胞凋亡。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-08-03 DOI:10.1016/j.mcp.2024.101978
Jiao Zhao, Jingru Zhang, Xiaojing Tong, Lili Zhao, Rong Cao
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引用次数: 0

摘要

卵巢癌(OC)是导致全球女性死亡的第五大常见病因。化疗耐药性是治疗失败的关键原因,会导致很高的死亡率。作为含三方基序(TRIM)蛋白家族的成员,三方基序47(TRIM47)在多种癌症的致癌和耐药过程中发挥着重要作用。本研究探讨了 TRIM47 对顺铂 (DDP) 化学敏感性和 OC 细胞凋亡的影响和机制。采用细胞计数试剂盒-8测定法评估了OC细胞的活力,采用流式细胞术、caspase-3和caspase-9活性、Bax和Bcl-2表达测定法评估了OC细胞的凋亡,同时采用qRT-PCR和Western印迹测定法评估了基因和蛋白的表达。与正常组织或亲代细胞系相比,TRIM47在OC患者的抗DDP组织和癌细胞系中的表达均明显增加。TRIM47水平的升高与OC患者的不良预后有关。功能测试表明,TRIM47 在体外和体内都促进了 DDP 抗性。内质网(ER)应激诱导剂妥卡霉素可挽救TRIM47诱导的OC细胞活力增加和凋亡减少,这表明TRIM47通过抑制ER应激抑制OC细胞凋亡。因此,TRIM47可作为治疗OC对DDP耐药的靶点。
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TRIM47 inhibits cisplatin chemosensitivity and endoplasmic reticulum stress-induced apoptosis of ovarian cancer cells

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.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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