Guan Ning, Huo Xiaochuan, Zhang Zhenxing, Zhang Shoudan, Luo Junsheng, Guo Wenshi
Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University, 2 Renmin Road, Jinzhou, 121001, China.
Tumour Biol. 2015 Sep;36(9):6789-95. doi: 10.1007/s13277-015-3387-1. Epub 2015 Apr 3.
Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor. Although the growth of the tumor cells in a relatively closed space may partially account for its malignancy, highly invasive nature of glioblastoma cells has been suggested to be the main reason for the failure of current therapeutic approaches. Ginsenoside Rh2 (GRh2) has recently been shown to significantly suppress the growth and survival of GBM through inhibiting epidermal growth factor receptor signaling, whereas its effects on the invasion and metastasis have not been examined. Here, we showed that GRh2 dose-dependently decreased GBM cell invasiveness in both scratch wound healing assay and Transwell cell migration assay. Moreover, the inhibitory effects of GRh2 on cell migration seemed to be conducted through decreased expression of matrix metalloproteinase (MMP)-13. Furthermore, using specific inhibitors, we found that GRh2 inhibited MMP13 through PI3k/Akt signaling pathway. Finally, high MMP13 levels were detected in GBM specimen from the patients. Together, these data suggest that GRh2 may suppress GBM migration through inhibiting Akt-mediated MMP13 activation. Thus, our data highlight a previous unappreciated role for GRh2 in suppressing GBM cell metastasis.
多形性胶质母细胞瘤（GBM）是原发性脑肿瘤中最恶性的类型。尽管肿瘤细胞在相对封闭的空间内生长可能部分解释了其恶性程度，但胶质母细胞瘤细胞的高度侵袭性被认为是当前治疗方法失败的主要原因。人参皂苷Rh2（GRh2）最近被证明可通过抑制表皮生长因子受体信号传导来显著抑制GBM的生长和存活，但其对侵袭和转移的影响尚未得到研究。在此，我们表明，在划痕伤口愈合试验和Transwell细胞迁移试验中，GRh2均呈剂量依赖性地降低GBM细胞的侵袭性。此外，GRh2对细胞迁移的抑制作用似乎是通过降低基质金属蛋白酶（MMP）-13的表达来实现的。此外，使用特异性抑制剂，我们发现GRh2通过PI3k/Akt信号通路抑制MMP13。最后，在患者的GBM标本中检测到高水平的MMP13。总之，这些数据表明GRh2可能通过抑制Akt介导的MMP13激活来抑制GBM迁移。因此，我们的数据突出了GRh2在抑制GBM细胞转移方面以前未被认识到的作用。
