Qiu Ming-Ke, Wang Shu-Qing, Pan Chang, Wang Yang, Quan Zhi-Wei, Liu Ying-Bin, Ou Jing-Min
Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Oncol Rep. 2017 May;37(5):2987-2993. doi: 10.3892/or.2017.5515. Epub 2017 Mar 21.
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.
研究了血管瘤（HA）中的基因表达情况，HA是婴儿期出现的良性、胎记样肿瘤，并在源自HA的内皮细胞（HDEC）中得到证实，同时还评估了这些细胞的增殖和凋亡情况。增殖期HA中，Rho相关蛋白激酶（ROCK）、血管内皮生长因子（VEGF）、Ki-67和增殖细胞核抗原的蛋白质和mRNA积累显著高于消退期HA。相反，p53和半胱天冬酶-3在消退期HA中的积累水平高于增殖期HA。增殖期HA的细胞凋亡指数较低，而在消退期HA中增加。用ROCK抑制剂Y-27632处理HDEC。Y-27632诱导p53表达并下调VEGF表达，显著抑制HA细胞的增殖并诱导细胞凋亡。在注射HDEC的裸鼠的HA中证实了抑制剂的作用。这些结果表明，ROCK参与了HA细胞中p53介导的凋亡和VEGF表达，并提示这种抑制作用可能用于未来的HA治疗。
