Li Shaoyi, Gao Yun, Ma Weining, Cheng Tianci, Liu Yunhui
Department of Neurosurgery, Shengjing Hospital of China Medical University, 36 Sanhaojie, Shenyang, 110004, China,
Tumour Biol. 2016 Dec;37:15477–15482. doi: 10.1007/s13277-015-3759-6. Epub 2015 Jul 29.
The malignancy of glioblastoma multiforme (GBM) is largely due to its local invasion and the presence of the tumor in the relatively restrained region in the brain. Hence, effective prevention of the cancer cell invasion is substantially critical for controlling the growth and deterioration of GBM. We have recently reported the role of ginsenoside Rh2 (GRh2) in suppressing the growth of GBM through EGFR/PI3k/Akt/mTor signaling pathways. Here, we further showed that GRh2 efficiently inhibited the cancer vascularization in vivo. In vitro, GRh2 dose-dependently inhibited the protein, but not messenger RNA (mRNA) of vascular endothelial growth factor A (VEGF-A) in GBM cells. We then examined the underlying mechanisms and found that GRh2 increased the levels of miR-497, which bound to 3'UTR of VEGF-A mRNA to inhibit its translation. Together, our data demonstrate a previously unappreciated role for GRh2 in inhibition of GBM-associated cancer vascularization, which may contribute to the effects of GRh2 on suppression of GBM cancer growth and invasion.
多形性胶质母细胞瘤（GBM）的恶性程度很大程度上归因于其局部侵袭以及肿瘤在大脑相对受限区域的存在。因此，有效预防癌细胞侵袭对于控制GBM的生长和恶化至关重要。我们最近报道了人参皂苷Rh2（GRh2）通过EGFR/PI3k/Akt/mTor信号通路抑制GBM生长的作用。在此，我们进一步表明GRh2在体内能有效抑制癌症血管生成。在体外，GRh2剂量依赖性地抑制GBM细胞中血管内皮生长因子A（VEGF-A）的蛋白质表达，但不影响其信使核糖核酸（mRNA）表达。然后我们研究了其潜在机制，发现GRh2增加了miR-497的水平，miR-497与VEGF-A mRNA的3'非翻译区（3'UTR）结合以抑制其翻译。总之，我们的数据证明了GRh2在抑制GBM相关癌症血管生成方面有一个以前未被认识到的作用，这可能有助于GRh2对GBM癌症生长和侵袭的抑制作用。
