ROCK inhibition as a potential therapeutic target involved in apoptosis in hemangioma
ROCK inhibition as a potential therapeutic target involved in apoptosis in hemangioma
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ROCK 抑制作为参与血管瘤细胞凋亡的潜在治疗靶点
DOI：
10.3892/or.2017.5515
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发表时间：
2017-05-01
期刊：
影响因子：
4.2
通讯作者：
Ou, Jing-Min
中科院分区：
文献类型：
--
作者：
Qiu, Ming-Ke;Wang, Shu-Qing;Ou, Jing-Min
检测了婴儿时期发生的血管瘤(HA)、良性胎记样瘤和HA来源的内皮细胞(HDEC)中的基因表达，并对其细胞增殖和凋亡进行了检测。Rho相关蛋白激酶(ROCK)、血管内皮生长因子(VEGF)、Ki-67和增殖细胞核抗原在增生期HAS中的蛋白和mRNA积聚显著高于消退期HAS。相反，P53和caspase-3在消退期比增殖期表现出更高的积聚水平。细胞凋亡指数在增殖期较低，消退期较高。用岩石抑制剂Y-27632处理高密度脂蛋白内皮细胞。Y-27632诱导HA细胞P53表达，下调血管内皮生长因子表达，显著抑制细胞增殖，诱导细胞凋亡。在注射HDEC的裸鼠的HAS中证实了这种抑制作用。这些结果表明ROCK参与了P53介导的HA细胞的凋亡和血管内皮生长因子的表达，提示这种抑制作用可能被用于未来的HA治疗。
Gene expression was examined in hemangiomas (HA), benign, birthmark-like tumors occurring in infancy, and confirmed in HA-derived endothelial cells (HDEC), for which cell proliferation and apoptosis were also assessed. Protein and mRNA accumulation of Rho-associated protein kinase (ROCK), vascular endothelial growth factor (VEGF), Ki-67 and proliferating cell nuclear antigen was significantly higher in proliferating phase HAs than in involuting phase HAs. In contrast, p53 and caspase-3 exhibited higher levels of accumulation in involuting than proliferating HAs. Cell apoptotic indexes were low in proliferating phase HAs and increased in involuting phase HAs. HDECs were treated with the ROCK inhibitor Y-27632. Y-27632 induced p53 expression and downregulated VEGF expression, significantly inhibited cell proliferation, and induced cell apoptosis in HA cells. The inhibitor effects were confirmed in HAs from HDEC-injected nude mice. These results indicated that ROCK is involved in p53-mediated apoptosis and VEGF expression in HA cells and suggested that such inhibition may be exploited for future HA therapies.