JAK2/STAT5信号通路作为犬肥大细胞瘤的潜在治疗靶点。
The JAK2/STAT5 signaling pathway as a potential therapeutic target in canine mastocytoma.
作者信息
Keller Alexandra, Wingelhofer Bettina, Peter Barbara, Bauer Karin, Berger Daniela, Gamperl Susanne, Reifinger Martin, Cerny-Reiterer Sabine, Moriggl Richard, Willmann Michael, Valent Peter, Hadzijusufovic Emir
机构信息
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
出版信息
Vet Comp Oncol. 2018 Mar;16(1):55-68. doi: 10.1111/vco.12311. Epub 2017 Apr 11.
BACKGROUND
Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma.
MATERIALS AND METHODS
We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1.
RESULTS
Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells.
CONCLUSION
The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.
背景
肥大细胞瘤是犬类中常被诊断出的皮肤肿瘤。在不可切除的肥大细胞瘤患者中，常应用新型靶向药物。转录因子STAT5与人类肿瘤性肥大细胞（MC）的存活有关。我们的研究评估了JAK2/STAT5通路作为犬肥大细胞瘤的一个新靶点。
材料与方法
我们使用了JAK2抑制剂（R763、TG101348、AZD1480、鲁索替尼）和STAT5抑制剂（匹莫齐特、白皮杉醇），并评估它们对两种肥大细胞瘤细胞系C2和NI-1的作用。
结果
在两种细胞系中均检测到活化的JAK2和STAT5。发现所应用的药物可抑制这些细胞的增殖和存活，其效力排序如下：R763 > TG101348 > AZD1480 > 匹莫齐特 > 鲁索替尼 > 白皮杉醇。此外，在NI-1细胞中，匹莫齐特与KIT靶向药物（托西替尼、马斯itinib、尼洛替尼、米哚妥林）联合使用可获得协同抗肿瘤作用。
结论
JAK2/STAT5通路是犬肥大细胞瘤治疗的一个新的潜在靶点。
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