Long-term in-vitro glucocorticoid treatment induces glucocorticoid resistance in canine mast cell tumors.

IF 1.1 4区 农林科学 Q2 Veterinary Canadian journal of veterinary research = Revue canadienne de recherche veterinaire Pub Date : 2021-10-01
Akira Matsuda
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Abstract

Although glucocorticoid administration has produced impressive results in treating canine mast cell tumors (MCTs), in some cases, glucocorticoids fail to reduce the tumor volume, leading to tumor relapse even after treatment. To date, mechanisms involved in glucocorticoid resistance in canine MCTs remain poorly defined. The objective of this study was to establish glucocorticoid-resistant canine MCT cell lines derived from glucocorticoid-sensitive cell lines after prolonged treatment with dexamethasone (Dex). Real-time polymerase chain reaction (RT-PCR) revealed that elevation of glucocorticoid receptor (GR)-regulated gene expression was suppressed in Dex-resistant cell lines after Dex stimulation compared with parent Dex-sensitive cell lines. This indicated that GR-regulated transcription was suppressed in Dex-resistant cell lines. Insufficient expression of GRs was not detected in Dex-resistant cell lines. Possible inhibitors of GR-regulated transcription were increased in mRNA expression in Dex-resistant cell lines. In addition, it was determined that mRNA expression of drug efflux pumps and anti-apoptosis factors was higher in Dex-resistant cell lines. In conclusion, glucocorticoid-resistant canine MCT cell lines have been established that are derived from glucocorticoid-sensitive cell lines. These cell lines suggest that multiple mechanisms contribute to glucocorticoid resistance in canine MCT cells. The mechanisms of glucocorticoid resistance after long-term treatment can be further investigated using these cell lines and a novel therapeutic strategy for glucocorticoid-resistant canine MCT cells can be developed.

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长期体外糖皮质激素治疗诱导犬肥大细胞肿瘤糖皮质激素耐药。
尽管糖皮质激素在治疗犬肥大细胞肿瘤(mct)方面取得了令人印象深刻的效果,但在某些情况下,糖皮质激素不能减少肿瘤体积,导致肿瘤在治疗后复发。迄今为止,犬mct中糖皮质激素耐药的机制仍然不明确。本研究的目的是在地塞米松(Dex)长期治疗后,从糖皮质激素敏感细胞系衍生出糖皮质激素耐药犬MCT细胞系。实时聚合酶链反应(RT-PCR)显示,与Dex敏感细胞株相比,Dex刺激后,Dex耐药细胞株糖皮质激素受体(GR)调控基因表达的升高受到抑制。这表明gr调控的转录在dex抗性细胞系中受到抑制。在dex耐药细胞系中未检测到GRs表达不足。在dex耐药细胞系中,可能的gr调控转录抑制剂的mRNA表达增加。此外,我们还发现dex耐药细胞株中药物外排泵和抗凋亡因子mRNA的表达较高。总之,糖皮质激素耐药犬MCT细胞系是由糖皮质激素敏感细胞系衍生而来。这些细胞系表明犬MCT细胞的糖皮质激素耐药有多种机制。利用这些细胞系可以进一步研究长期治疗后糖皮质激素耐药的机制,并为糖皮质激素耐药的犬MCT细胞开发新的治疗策略。
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来源期刊
CiteScore
1.80
自引率
0.00%
发文量
58
审稿时长
>24 weeks
期刊介绍: The Canadian Journal of Veterinary Research, published by the Canadian Veterinary Medical Association, is Canada''s only veterinary research publication. This quarterly peer-reviewed online-only journal has earned a wide international readership through the publishing of high quality scientific papers in the field of veterinary medicine. The Journal publishes the results of original research in veterinary and comparative medicine.
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