Department of Cardiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
Steroids. 2013 Oct;78(10):1041-5. doi: 10.1016/j.steroids.2013.06.008. Epub 2013 Jul 4.
Malignant gliomas are the most devastating and aggressive brain tumors affecting the central nervous system. The insidious growth and infiltration are the most prominent characteristics of malignant gliomas, which render the current therapies for malignant gliomas including surgery, radiation and chemotherapy unsuccessful. Inhibition of infiltration as well as proliferation in combination with surgery might be more effective in the treatment of malignant gliomas. In the current study, we demonstrate the alphaxalone (3-hydroxypregnane-11,20-dione) could effectively inhibit the proliferation of C6 glioma cells in a concentration dependent manner. Moreover, this compound could also suppress the migration and invasion of C6 glioma cells at a concentration without causing significant cytotoxicity. Except the in vitro anti-glioma activity, alphaxalone effectively delayed the growth of rat C6 malignant glioma xenografts in vivo. Together, these findings suggest alphaxalone might be a promising candidate for the treatment of malignant gliomas and may also provide helpful clues for anti-glioma drugs development in future.
恶性脑胶质瘤是中枢神经系统中最具破坏性和侵袭性的脑肿瘤。恶性脑胶质瘤最显著的特征是其侵袭性生长和浸润,这使得目前针对恶性脑胶质瘤的治疗方法,包括手术、放疗和化疗,都无法取得成功。抑制浸润和增殖并结合手术可能更有效地治疗恶性脑胶质瘤。在本研究中,我们证明了α-羟基孕烷-11,20-二酮(alphaxalone)能够以浓度依赖的方式有效抑制 C6 神经胶质瘤细胞的增殖。此外,该化合物还可以抑制 C6 神经胶质瘤细胞的迁移和侵袭,而不会引起明显的细胞毒性。除了体外抗神经胶质瘤活性外,α-羟基孕烷-11,20-二酮还能有效抑制体内大鼠 C6 恶性神经胶质瘤异种移植物的生长。综上所述,这些发现表明,α-羟基孕烷-11,20-二酮可能是治疗恶性脑胶质瘤的一种有前途的候选药物,也可能为未来抗脑胶质瘤药物的开发提供有价值的线索。