The inhibition of BDNF/TrkB/PI3K/Akt signal mediated by AG1601 promotes apoptosis in malignant glioma

Abstract

Malignant glioma is the most aggressive primary brain tumor and has a poor survival rate. Even if extensive methods are preformed to treat glioma, the mortality rate is still very high. It is necessary for discovering and developing new drugs for malignant glioma treatment. AG1601 is one of AG‐series drugs, including AG1031 and AG1503, and it has been optimized on the original basis. In our study, we found that AG1601 markedly inhibited proliferation and promoted C6 glioma cell apoptosis in vitro. AG1601 also reduced the size and weight of glioma in vivo. The growth ability of glioma was significantly inhibited after treatment with AG1601. It also showed that the expression levels of BDNF/TrkB/PI3K/Akt signal related proteins were obviously decreased in C6 glioma cells after treatment with AG1601 in vivo and in vitro. We also found that BDNF, as the activator of BDNF/TrkB/PI3K/Akt signal, reversed the anti‐proliferation and pro‐apoptosis of C6 glioma cells caused by AG1601. K252a, a specific inhibitor of TrkB, and AG1601 in combination aggravated C6 glioma cell apoptosis. These results indicate that AG1601 has good effects on the anti‐proliferation and pro‐apoptosis of malignant glioma via BDNF/TrkB/PI3K/Akt signal and could be considered as a potential drug in treating malignant glioma.

Suppressive effects of bilobalide on depression-like behaviors induced by chronic unpredictable mild stress in mice

“…11 Also, BDNF can activate three major downstream signals through Trk-B, which include AKT. 12 GSK3β is a downstream target of AKT. Activated AKT phosphorylates GSK3β, leading to GSK3β inactivation, then catalyzes β-catenin, which is involved in the cell cycle and neural formation.…”