首页> 外文期刊>Annals of surgical oncology >Suberoyl bishydroxamic acid activates notch1 signaling and suppresses tumor progression in an animal model of medullary thyroid carcinoma.
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Suberoyl bishydroxamic acid activates notch1 signaling and suppresses tumor progression in an animal model of medullary thyroid carcinoma.

机译:在甲状腺髓样癌的动物模型中,Suberoyl bishydroxamicamicate激活notch1信号传导并抑制肿瘤进展。

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BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy that frequently metastasizes and has few treatments. This study was aimed at assessing the antitumor effects of suberoyl bishydroxamic acid (SBHA) in an in vivo model of MTC. METHODS: Nude mice were injected with human MTC cells, and the groups were treated with SBHA (200 mg/kg) or vehicle (dimethyl sulfoxide) in saline injection every other day for 12 days. Tumors were measured every 4 days and collected at 12 days for Western blot analysis. RESULTS: Treatment with SBHA resulted in an average 55% inhibition of tumor growth in the treatment group (P < .05). Analysis of SBHA-treated MTC tumors revealed a marked increase in the active form of Notch1 (NICD) with a concomitant decrease in achaete-scute complex-like 1 (ASCL1), a downstream target of Notch1 signaling, as well as the neuroendocrine tumor marker chromogranin A. Importantly, SBHA treatment resulted in an increase in protein levels of p21(CIP1/WAF1), p27(KIP1), cleaved caspase-9, cleaved caspase-3, and cleaved poly ADP-ribose polymerase and concomitant with a decrease in cyclin D1 and cyclin B1, indicating that the growth inhibition was due to both cell cycle arrest and apoptosis. Moreover, SBHA downregulated cell survival proteins Bcl-2 and Bcl-X(L), but upregulated apoptotic proteins Bax, Bad, and Bmf. CONCLUSION: These results demonstrate that SBHA inhibits MTC growth in vivo. SBHA is a promising candidate for further preclinical and clinical studies in MTC.
机译:背景:甲状腺髓样癌(MTC)是一种神经内分泌恶性肿瘤,其经常转移且几乎没有治疗方法。这项研究旨在评估MTC体内模型中的Suberoyl双异羟肟酸(SBHA)的抗肿瘤作用。方法:给裸鼠注射人MTC细胞,每隔一天注射SBHA(200 mg / kg)或溶媒(二甲亚砜)注射生理盐水,每组12天。每4天测量一次肿瘤,每12天收集一次以进行蛋白质印迹分析。结果:SBHA治疗组平均抑制肿瘤生长55%(P <.05)。对SBHA治疗的MTC肿瘤的分析显示,Notch1(NICD)的活性形式显着增加,而achaete-scute复合物样1(ASCL1)(Notch1信号的下游靶标)以及神经内分泌肿瘤标志物随之减少重要的是,SBHA处理导致蛋白水平p21(CIP1 / WAF1),p27(KIP1),裂解的caspase-9,裂解的caspase-3和裂解的多聚ADP-核糖聚合酶的蛋白水平增加,并且随之降低细胞周期蛋白D1和细胞周期蛋白B1,表明生长抑制是由于细胞周期停滞和凋亡。此外,SBHA下调细胞存活蛋白Bcl-2和Bcl-X(L),但上调凋亡蛋白Bax,Bad和Bmf。结论:这些结果表明SBHA在体内抑制MTC的生长。 SBHA是MTC进一步临床前和临床研究的有希望的候选人。

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