Sophocarpine inhibits the progression of glioblastoma via PTEN/PI3K/Akt signaling pathway.

Abstract

Glioblastoma multiforme (GBM) is the most fatal primary brain tumor which lacks effective treatment drugs. Alkaloids are known as a class of potential anti-tumor agents. Sophocarpine, a tetracyclic quinazoline alkaloid derived from Sophora alopecuroides L., possesses several pharmacological effects including anti-tumor effects in some malignancies. However, the effect and mechanism of sophocarpine on GBM remains to be explored. In this study, based on in vitro experiments, we found that sophocarpine significantly inhibited the viability, proliferation and migration of GBM cells including U251 and C6 cells in a dose- and time-dependent manner. Besides, sophocarpine arrested GBM cell cycle in G0/G1 phase and induced their apoptosis. Subsequently, we found that sophocarpine upregulated the expression of PTEN, a GBM tumor suppressor, and downregulated PI3K/Akt signaling in GBM cells. Moreover, inactivating of PTEN with bpV(phen) trihydrate partially restored the anti-GBM effects of sophocarpine via PI3K/Akt signaling. Finally, sophocarpine significantly inhibited the growth of tumor both in subcutaneous and orthotopic U251 xenograft GBM model in nude mice via PTEN/PI3K/Akt axis. Taken together, these results suggested that sophocarpine impeded GBM progression via PTEN/PI3K/Akt axis both in vitro and in vivo, providing with a promising therapy for treating GBM.