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酪氨酸激酶抑制剂甲磺酸马西替尼对犬乳腺肿瘤细胞系的影响。

Effects of Tyrosine Kinase Inhibitor-masitinib Mesylate on Canine Mammary Tumour Cell Lines.

作者信息

Ustun-Alkan Fulya, Bakırel Tülay, Üstüner Oya, Anlas Ceren, Cinar Suzan, Yıldırım Funda, Gürel Aydın

机构信息

Department of Pharmacology and Toxicology, Istanbul, Turkey.

Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093, Istanbul, Turkey.

出版信息

J Vet Res. 2021 Jul 24;65(3):351-359. doi: 10.2478/jvetres-2021-042. eCollection 2021 Sep.

DOI:10.2478/jvetres-2021-042
PMID:34917849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8643080/
Abstract

INTRODUCTION

Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib has previously been investigated in various cancers; however, its potential anticancer effect in canine mammary tumours (CMTs) is unknown. In the present paper, we investigated the antiproliferative effect of masitinib in CMT cells and its possible mechanisms of action.

MATERIAL AND METHODS

The effect of masitinib on the proliferation of CMT-U27 and CMT-U309 cells was assessed by MTT assay and DNA fragmentation. Flow cytometric analysis was used to measure the effect of masitinib on apoptosis and the cell cycle. Additionally, vascular endothelial growth factor levels (VEGF) were measured, and the proliferation marker Ki-67 was visualised in immunocytochemical stainings in CMT cells.

RESULTS

Treatment with masitinib inhibited the proliferation of CMT cells in a concentration-dependent manner. Maximal apoptotic activity and DNA fragmentation were observed at approximately IC of masitinib in both cell lines. In addition, cell cycle distribution was altered and VEGF levels and Ki-67 proliferation indices were decreased in masitinib-treated cells in comparison with control cells.

CONCLUSION

In this study, masitinib suppressed cell proliferation concomitantly induction of apoptosis and cell cycle arrest by decreasing VEGF levels and the Ki-67 proliferation index in CMT-U27 and CMT-U309 cells , suggesting its potential as a therapeutic tool in the clinical setting of mammary cancer treatment in dogs.

摘要

引言

甲磺酸马西替尼是一种c-KIT受体的选择性酪氨酸激酶抑制剂，用于治疗犬类肥大细胞瘤。马西替尼此前已在多种癌症中进行过研究；然而，其在犬乳腺肿瘤（CMT）中的潜在抗癌作用尚不清楚。在本文中，我们研究了马西替尼对CMT细胞的抗增殖作用及其可能的作用机制。

材料与方法

通过MTT法和DNA片段化评估马西替尼对CMT-U27和CMT-U309细胞增殖的影响。采用流式细胞术分析马西替尼对细胞凋亡和细胞周期的影响。此外，还测量了血管内皮生长因子水平（VEGF），并在CMT细胞的免疫细胞化学染色中观察增殖标志物Ki-67。

结果

马西替尼处理以浓度依赖性方式抑制CMT细胞的增殖。在两种细胞系中，在马西替尼的约IC时观察到最大凋亡活性和DNA片段化。此外，与对照细胞相比，马西替尼处理的细胞中细胞周期分布发生改变，VEGF水平和Ki-67增殖指数降低。

结论

在本研究中，马西替尼通过降低CMT-U27和CMT-U309细胞中的VEGF水平和Ki-67增殖指数，抑制细胞增殖并伴随诱导细胞凋亡和细胞周期停滞，表明其在犬乳腺癌治疗临床环境中作为治疗工具的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/bbcf21228fc3/jvetres-65-351-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/9d56cd57692f/jvetres-65-351-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/3c5dae355e71/jvetres-65-351-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/18cce32d0302/jvetres-65-351-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/bbcf21228fc3/jvetres-65-351-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/9d56cd57692f/jvetres-65-351-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/fa50457b5264/jvetres-65-351-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65c4/8643080/14db93343e3c/jvetres-65-351-g003.jpg
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