Enhancing effect of DHEA ON DbcAMP-induced cell differentiation / 中国药理学通报

ABSTRACT

Aim To observe whether DHEA has enhancing effect on DbcAMP -induced differentiation of NG108-15 cells, including neurite outgrowth, and study its possible mechanisms. Methods NG108-15 cells (a h ybrid cell line of mouse neuroblastoma and rat glioma) were used as a substitute for primary culture neuron in vitro. The morphology of NG108-15 cells was o bserved and neurite outgrowth was determined in an inversed microscope after treatme nt with various drugs. Gelatin-substrate gel electrophoresis was used to detect gelatinases (MMP-9 and MMP-2). Results ① DHEA and DbcAMP inhibited NG108-15 proliferation.②DHEA had enhancing effect on the promoting activity of neuronal differentiation and neurite outgrowth by DbcAMP. DbcAMP could increase neurite elongation of NG108-15 cells. Compared with this, the combined treatment with DHEA and DbcAMP significantly enhanced the neurite outgrowth of NG108-15 cells, including neurite length and numbers of cells with neurite, in a DHEA dose-dependent manner. ③ MMPs were involved in neuronal differentiation. DbcAMP induced the increase in MMP-9 and MMP-2 activities and such elevation was enhanced by DHEA in a dose-dependent manner. Conclusion DHEA enhances the effect of DbcAMP in promoting the neurite outgrowth of NG108-15 cells, which might be related to the increase in MMP-9 and MMP-2 activities.