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长效环氧化酶-2抑制剂马罗昔布(Trocoxil™)在体外对犬癌细胞系和癌症干细胞具有抗增殖和促凋亡作用。

The long-acting COX-2 inhibitor mavacoxib (Trocoxil™) has anti-proliferative and pro-apoptotic effects on canine cancer cell lines and cancer stem cells in vitro.

作者信息

Pang Lisa Y, Argyle Sally A, Kamida Ayako, Morrison Katherine O'Neill, Argyle David J

出版信息

BMC Vet Res. 2014 Sep 5;10:184. doi: 10.1186/s12917-014-0184-9.

Abstract

BACKGROUND

The NSAID mavacoxib (Trocoxcil™) is a recently described selective COX-2 inhibitor used for the management of inflammatory disease in dogs. It has a long plasma half-life, requiring less frequent dosing and supporting increased owner compliance in treating their dogs. Although the use of NSAIDs has been described in cancer treatment in dogs, there are no studies to date that have examined the utility of mavacoxib specifically.

RESULTS

In this study we compared the in vitro activity of a short-acting non-selective COX inhibitor (carprofen) with mavacoxib, on cancer cell and cancer stem cell survival. We demonstrate that mavacoxib has a direct cell killing effect on cancer cells, increases apoptosis in cancer cells in a manner that may be independent of caspase activity, and has an inhibitory effect on cell migration. Importantly, we demonstrate that cancer stem cells derived from osteosarcoma cell lines are sensitive to the cytotoxic effect of mavacoxib.

CONCLUSIONS

Both NSAIDs can inhibit cancer cell proliferation and induce apoptosis in vitro. Importantly, cancer stem cells derived from an osteosarcoma cell line are sensitive to the cytotoxic effect of mavacoxib. Our results suggest that mavacoxib has anti-tumour effects and that this in vitro anti-cancer activity warrants further study.

摘要

背景

非甾体抗炎药马瓦昔布(Trocoxcil™)是一种最近被描述的选择性COX - 2抑制剂,用于治疗犬类炎症性疾病。它的血浆半衰期长,给药频率较低,有助于提高犬主治疗其宠物犬的依从性。虽然已有关于非甾体抗炎药在犬类癌症治疗中的应用报道,但迄今为止尚无专门研究马瓦昔布效用的研究。

结果

在本研究中,我们比较了短效非选择性COX抑制剂(卡洛芬)与马瓦昔布对癌细胞和癌症干细胞存活的体外活性。我们证明马瓦昔布对癌细胞有直接的细胞杀伤作用,以可能独立于半胱天冬酶活性的方式增加癌细胞凋亡,并对细胞迁移有抑制作用。重要的是,我们证明源自骨肉瘤细胞系的癌症干细胞对马瓦昔布的细胞毒性作用敏感。

结论

两种非甾体抗炎药均可在体外抑制癌细胞增殖并诱导凋亡。重要的是,源自骨肉瘤细胞系的癌症干细胞对马瓦昔布的细胞毒性作用敏感。我们的结果表明马瓦昔布具有抗肿瘤作用,这种体外抗癌活性值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4748/4172958/34442c33fbcc/12917_2014_184_Fig3_HTML.jpg

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