Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China.
PLoS One. 2013 Aug 21;8(8):e72079. doi: 10.1371/journal.pone.0072079. eCollection 2013.
Mitogen-activated protein kinases/Extracellular signal-regulated kinase (MAPK/ERK) pathway is essential for migration and invasion of malignant glioma. It is efficient to inhibit migration and invasion of glioma cells by targeting this pathway. Oleanolic acid (OA) has been well demonstrated to suppress survival, growth and angiogenesis of glioma cells. However, it is still unknown if OA affects the migration and invasion of glioma cells. We utilized U-87 MG glioma cell lines and primary glioma cells from patients to study the effect of OA on migration and invasion of glioma cells with multidisciplinary approaches. In this study, we found that OA significantly decreased the ability of glioma cells to migrate and invade. Epithelial-mesenchymal transition (EMT) of glioma cells was also suppressed by OA treatment. Furthermore, MAPK/ERK pathway was greatly inhibited in glioma cells under OA treatment. MAPK/ERK reactivation induced by a recombinant lentiviral vector, Lv-MEK, was able to rescue the inhibitory effect of OA on migration and invasion of glioma cells. Taken together, we provided evidences that OA was a MAPK/ERK pathway-targeting anti-tumor agent. Although the concentrations we used exceeded its physiological level, OA may be used to prevent migration and invasion of glioma cells by developing its derivatives with enhanced bioactivity.
丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）通路对于恶性脑胶质瘤的迁移和侵袭至关重要。通过靶向该通路，可以有效地抑制胶质瘤细胞的迁移和侵袭。齐墩果酸（OA）已被证明能抑制胶质瘤细胞的存活、生长和血管生成。然而，OA 是否影响胶质瘤细胞的迁移和侵袭仍不清楚。我们利用 U-87 MG 脑胶质瘤细胞系和来自患者的原代胶质瘤细胞，采用多学科方法研究 OA 对胶质瘤细胞迁移和侵袭的影响。在这项研究中，我们发现 OA 显著降低了胶质瘤细胞的迁移和侵袭能力。OA 处理还抑制了胶质瘤细胞的上皮-间充质转化（EMT）。此外，OA 处理还极大地抑制了胶质瘤细胞中的 MAPK/ERK 通路。由重组慢病毒载体 Lv-MEK 诱导的 MAPK/ERK 再激活能够挽救 OA 对胶质瘤细胞迁移和侵袭的抑制作用。总之，我们提供了证据表明 OA 是一种靶向 MAPK/ERK 通路的抗肿瘤药物。尽管我们使用的浓度超过了其生理水平，但通过开发具有增强生物活性的 OA 衍生物，OA 可能被用于预防胶质瘤细胞的迁移和侵袭。
