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糠酸莫米松通过调节PI3K信号通路抑制儿童急性白血病细胞的生长。

Mometasone furoate inhibits growth of acute leukemia cells in childhood by regulating PI3K signaling pathway.

作者信息

Wang Xiaojing, Shi Jianli, Gong Deqiang

机构信息

a Department of Pediatrics , No. Four Hospital of Jinan , Jinan , Shandong 250000 , People's Republic of China.

出版信息

Hematology. 2018 Sep;23(8):478-485. doi: 10.1080/10245332.2018.1436395. Epub 2018 Feb 8.

Abstract

OBJECTIVES

Acute lymphoblastic leukemia (ALL) is the most common cancer before the age of 15 years, seriously endangering the health of children. The main treatment for Childhood ALL was pharmacotherapy. But these drugs have many side effects and some of them could develop drug resistance quickly. Mometasone furoate (MF) is an efficient glucocorticoid for topical treatment of inflammation on the skin, lung and nose.

METHODS

In this study, we investigated whether the MF had effects on ALL cells proliferation and migration.

RESULTS

The CCK-8 proliferation test showed that the cell viability was the lowest at 25 nM MF treatment and the increased OD value was time-dependent. In transwell assay, the number of CCRF-CEM cells was reduced in MF treated group. We found the expression of anti-apoptotic protein bcl-2 decreased the expression of pro-apoptotic protein caspase3 and bax increased in CCRF-CEM cell line treated with MF. The expression of p-AKT, p-mTOR, p70S6 K, vascular endothelial growth factor and CyclinD1 were decreased in MF treated group.

CONCLUSION

This study reveals that MF can inhibit proliferation and invasion/migration and induce apoptosis in Childhood ALL cells, which may be regulated by Phosphatidylinositol 3-kinase signaling pathway. These results suggest MF may be a potential new drug target for clinical ALL treatment.

摘要

目的

急性淋巴细胞白血病(ALL)是15岁以前最常见的癌症,严重危及儿童健康。儿童ALL的主要治疗方法是药物治疗。但这些药物有许多副作用,其中一些可能很快产生耐药性。糠酸莫米松(MF)是一种有效的糖皮质激素,用于局部治疗皮肤、肺部和鼻部的炎症。

方法

在本研究中,我们研究了MF是否对ALL细胞的增殖和迁移有影响。

结果

CCK-8增殖试验表明,在25 nM MF处理下细胞活力最低,且OD值的增加呈时间依赖性。在Transwell试验中,MF处理组的CCRF-CEM细胞数量减少。我们发现,在用MF处理的CCRF-CEM细胞系中,抗凋亡蛋白bcl-2的表达降低,促凋亡蛋白caspase3的表达降低,bax的表达增加。MF处理组中p-AKT、p-mTOR、p70S6 K、血管内皮生长因子和细胞周期蛋白D1的表达均降低。

结论

本研究表明,MF可抑制儿童ALL细胞的增殖、侵袭/迁移并诱导其凋亡,这可能受磷脂酰肌醇3激酶信号通路调控。这些结果表明,MF可能是临床ALL治疗的潜在新药靶点。

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