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Table 1 Effects of low and high concentrations of P4 on glioblastoma cells in in vitro and in vivo models

From: Impact of sex in the prevalence and progression of glioblastomas: the role of gonadal steroid hormones

P4
Low doses High doses
• In vitro effects • In vitro effects
 - Induces proliferation through PR actions (10 nM) (ref [8])  - Decreases cell viability (20–80 μM) (ref [9])
 - Increases the expression of EGFR and cyclin D1 through its PR and the recruitment of steroid receptor coactivator-1 (SRC-1) (10 nM) (ref [10])  - Enhances toxicity of TMZ (5 and 80 μM) (ref [11])
 - Induces the expression of progesterone-induced blocking factor (PIBF) (10 nM) (ref [12])  - Changes in detoxification mechanisms, stress, immune response, and glucose metabolism (100 and 300 μM) (ref [13])
 - Stimulates the unphosphorylated state of cofilin (10 nM) (ref [14])  - Reduction of glycolytic metabolism by decreasing the Glut1 expression (8 and 100 μM) (ref [15])
 - Induces migration and invasion through PR actions (10 nM) (ref [14])
 - Increases the number of glioma stem cells from U251 cells (10 nM) (ref [16])
 - Allopregnanolone and 5alpha-dihydroprogesterone (P4 metabolites) increase the number of glioblastoma cells (10 nM) (refs [17, 18])
 - 5alpha-dihydroprogesterone increases the migration of glioblastoma cells (10 nM) (ref [18])
• In vivo effects • In vivo effects
 - Increases the area and infiltration of tumor through PR actions (1 mg) (refs [8, 19, 20])  - Reduction of tumor volume (8 and 100 μM) (ref [9]) (100 and 200 μM) (ref [15])
 - Induction of cell senescence by attenuating the signaling pathway PI3K/Akt/mTOR (8 and 100 μM) (ref [9])