Therapeutic trial of fluvastatin in a cell line xenograft model of canine mammary gland cancer.

IF 2.3 2区 农林科学 Q1 VETERINARY SCIENCES Veterinary and comparative oncology Pub Date : 2023-12-01 Epub Date: 2023-09-14 DOI:10.1111/vco.12926
Mohamed Issam Atmane, Anne-Laurence Vigneau, Francis Beaudry, Charlène Rico, Derek Boerboom, Marilène Paquet
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Abstract

The Hippo signalling pathway is involved in breast cancer and canine mammary tumour (CMT). This study sought to evaluate the efficacy of fluvastatin on the Hippo pathway and its main effectors, YAP and TAZ, in vivo in a murine CMT cell line xenograft model. On treatment day 1, mice were divided into four groups: vehicle, fluvastatin, doxorubicin or a combination therapy. Tumour volumes were monitored with callipers and tissues harvested on day 28th of treatment. Histopathological examination of tumour tissues and major organs was performed as well as tumour evaluation of necrosis, apoptosis, cellular proliferation, expression of YAP, TAZ and the mRNA levels of four of their target genes (CTGF, CYR61, ANKRD1 and RHAMM2). Results showed a statistically significant variation in tumour volumes only for the combination therapy and final tumour weight only for the doxorubicin group compared to control. There was no significant difference in tumour necrosis, expression of CC3, ki-67, YAP and TAZ measured by immunohistochemistry and in the mRNA levels of the target genes. Unexpectedly, lung metastases were found in the control group (9) and not in the fluvastatin treated group (7). In addition, mass spectrometry-based quantification of fluvastatin reveals concentrations comparable to levels reported to exert therapeutic effects. This study shows that fluvastatin tumours concentration reached therapeutic levels without having an effect on the hippo pathway or various tumour parameters. Interestingly, only the control group had lung metastases. This study is the first to explore the repurposing of statins for cancer treatment in veterinary medicine.

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氟伐他汀在犬乳腺癌细胞系异种移植模型中的治疗试验。
Hippo信号通路与乳腺癌和犬乳腺肿瘤(CMT)有关。本研究旨在评估氟伐他汀对小鼠CMT细胞系异种移植模型体内Hippo通路及其主要效应物YAP和TAZ的疗效。在治疗第1天,小鼠被分为四组:药物、氟伐他汀、阿霉素或联合治疗。在治疗第28天用卡尺和收集的组织监测肿瘤体积。对肿瘤组织及主要脏器进行组织病理学检查,对坏死、凋亡、细胞增殖、YAP、TAZ表达及4个靶基因(CTGF、CYR61、ANKRD1、RHAMM2) mRNA水平进行肿瘤评价。结果显示,与对照组相比,仅联合治疗组的肿瘤体积和仅阿霉素组的最终肿瘤重量在统计学上有显著差异。两组肿瘤坏死、免疫组化检测CC3、ki-67、YAP、TAZ的表达及靶基因mRNA水平差异无统计学意义。出乎意料的是,在对照组中发现了肺转移(9),而在氟伐他汀治疗组中没有发现(7)。此外,基于质谱的氟伐他汀定量显示,其浓度与报道的发挥治疗作用的水平相当。该研究表明,氟伐他汀肿瘤浓度达到治疗水平,而不会对河马通路或各种肿瘤参数产生影响。有趣的是,只有对照组有肺转移。这项研究首次探索了他汀类药物在兽医学癌症治疗中的再利用。
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来源期刊
Veterinary and comparative oncology
Veterinary and comparative oncology 农林科学-兽医学
CiteScore
4.80
自引率
9.50%
发文量
75
审稿时长
>24 weeks
期刊介绍: Veterinary and Comparative Oncology (VCO) is an international, peer-reviewed journal integrating clinical and scientific information from a variety of related disciplines and from worldwide sources for all veterinary oncologists and cancer researchers concerned with aetiology, diagnosis and clinical course of cancer in domestic animals and its prevention. With the ultimate aim of diminishing suffering from cancer, the journal supports the transfer of knowledge in all aspects of veterinary oncology, from the application of new laboratory technology to cancer prevention, early detection, diagnosis and therapy. In addition to original articles, the journal publishes solicited editorials, review articles, commentary, correspondence and abstracts from the published literature. Accordingly, studies describing laboratory work performed exclusively in purpose-bred domestic animals (e.g. dogs, cats, horses) will not be considered.
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