Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Journal of Cellular and Molecular Medicine Pub Date : 2023-06-19 DOI:10.1111/jcmm.17717
Chen-Hui Lu, Shu-Han Yu, Ching-Ho Wu, Jason Lih-Seng Yeh, Hui-Wen Chang, Chian-Ren Jeng, Yen-Chen Chang
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Abstract

Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.

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选择性环氧合酶-2抑制剂罗苯那昔布对猫注射部位肉瘤原代细胞的影响
猫注射部位肉瘤(FISSs)是一种高度侵袭性的恶性间充质肿瘤,起源于猫的注射部位。虽然FISS的肿瘤发生机制尚不清楚,但已有共识认为FISS与注射相关创伤和外来化学物质刺激引起的慢性炎症有关。慢性炎症可以为肿瘤的发展提供适当的微环境,这是许多肿瘤发生的危险因素之一。为了研究FISS的肿瘤发生并筛选其潜在的治疗靶点,我们选择了一种炎症增强酶环氧化酶-2 (COX-2)作为本研究的靶点。体外实验使用FISS和正常组织来源的原代细胞和robenacoxib(一种高选择性COX-2抑制剂)进行。结果表明,COX-2在福尔马林固定和石蜡包埋的FISS组织和FISS原代细胞中均可检测到表达。罗苯那昔布能抑制fiss原代细胞的活力、迁移和集落形成,并能促进细胞凋亡,且呈剂量依赖性。然而,不同细胞系的FISS原代细胞对罗苯那昔布的敏感性不同,且与COX-2的表达不完全相关。我们的研究结果表明,COX-2抑制剂可能是潜在的辅助治疗fiss。
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来源期刊
CiteScore
10.00
自引率
1.90%
发文量
496
审稿时长
28 weeks
期刊介绍: Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.
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