Allopregnanolone promotes proliferation and differential gene expression in human glioblastoma cells

作者：Zamora Sanchez Carmen J; Han**erg Pastor Valeria; Salido Guadarrama Ivan; Rodriguez Dorantes Mauricio; Camacho Arroyo Ignacio^*

来源：Steroids, 2017, 119: 36-42.

DOI：10.1016/j.steroids.2017.01.004

• Allopregnanolone
• Progesterone
• 5 alpha-Reductase
• Proliferation
• Human astrocytomas
• Glioblastomas

Allopregnanolone (3 alpha-THP) is one of the main reduced progesterone (P-4) metabolites that is recognized as a neuroprotective and myelinating agent. 3 alpha-THP also induces proliferation of different neural cells. It has been shown that P-4 favors the progression of glioblastomas (GBM), the most common and aggressive primary brain tumors. However, the role of 3 alpha-THP in the growth of GBMs is unknown. Here, we studied the effects of 3 alpha-THP on the number of cells, proliferation and gene expression in U87 cell line derived from a human GBM. 3 alpha-THP (10, 100 nM and 1 mu M) increased the number of U87 cells, and at 10 nM exerted a similar increase in both the number of total and proliferative U87 cells as compared with P-4 (10 nM). Interestingly, finasteride (F; 100 nM), an inhibitor of 5 alpha-reductase (5 alpha R), an enzyme necessary to metabolize P-4 and produce 3 alpha-THP, blocked the increase in the number of U87 cells induced by P-4. By using RT-qPCR, we determined that U87 cells express 5 alpha-R isoenzymes 1 and 2 (5 alpha R1 and 5 alpha R2), being 5 alpha R1 the predominant one in these cells. 3 alpha-THP (10 nM) increased the expression of TGF beta 1, EGFR, VEGF and cyclin D1 genes. P-4 increased TGF beta 1 and EGFR expression, and this effect was blocked by F. These data provide evidence that P-4, through its metabolite 3 alpha-THP, can promote in part cell proliferation of human GBM cells by changing the expression of genes involved in tumor progression.

• 出版日期2017-3