To explore the inhibitory effect of DIM-C-pPhOH (NR4A1 antagonist) on proliferation, migration and invasion of glioma cells and its mechanism, as well as the effect on the survival time and tumor of glioma mouse model.

Cell viability of glioma cell lines (GL261, U251, U118) treated with DIM-C-pPhOH for 48 h and then detected cell viability and IC₅₀ by CellTiter. The effect of DIM-C-pPhOH on invasion and migration of U251 cell line was studied by scratch experiment and 3D-invasion experiment. Meanwhile, DIM-C-pPhOH inhibited the TGF-β-induced nucleotide expression of NR4A1. Intraperitoneal injection of DIM-C-pPhOH in mice glioma model was used to simulate in vivo environment to observe the survival curve and its effect on tumor growth. Western blotting showed that DIM-C-pPhOH could significantly inhibit the expression of Akt and p70S6K proteins, and induce autophagy by inhibiting the PI3K/Akt/mTOR/p70S6K signaling pathway.

After DIM-C-pPhOH treatment, the cell activity of glioma cell lines decreased significantly with the increase of drug concentration, and the IC₅₀ of U251, GL261 and U118 gloma cell lines were 5.76, 6.87, and 9.93 μmol/L, respectively. The migration and invasion ability of U251 cells in glioma decreased significantly after DIM-C-pPhOH (10 μmol/L) treatment. In the mouse glioma model, the survival time of the drug treatment group was prolonged and tumor growth was inhibited. Western blotting showed that DIM-C-pPhOH could significantly inhibit the expression of Akt and P70S6K, and induce autophagy by inhibiting PI3K/Akt/mTOR/p70S6K signaling pathway.

DIM-C-pPhOH can reduce the migration and invasion of glioma, prolong the survival time of mouse glioma model and inhibit tumor growth. The underlying mechanism may be related to autophagy induced by DIM-C-pPhOH.