Oridonin inhibits growth and induces apoptosis of human neurocytoma cells via the Wnt/[beta]-catenin pathway

Central neurocytoma (CN) is a rare periventricular tumor of the central nervous system in young adults. Typically, patients with CN exhibit a favorable prognosis, but in certain cases the clinical course is more aggressive. Therefore, investigating effective therapeutic approaches is important. Oridonin has attracted attention due to its antitumor activities. However, the role of oridonin in tumorigenesis and progression remains unknown. The present study examined the antitumor function of oridonin in CN cells, and investigated the underlying molecular mechanism. An MTT assay suggested that treatment with oridonin was able to significantly inhibit the proliferation of CN cells. The annexin V-fluorescein isothiocyanate/propidium iodide assay and western blot analysis demonstrated that oridonin was able to induce apoptosis and alter the expression of apoptosis-associated proteins by downregulating anti-apoptotic protein, B-cell lymphoma-2 (Bcl-2), and upregulating pro-apoptosis proteins, Bcl-2-like protein 4, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase 1. Subsequently, the Wnt/[beta]-catenin signaling pathway was examined. Western blot analysis indicated that oridonin markedly decreased the expression of [beta]-catenin, cyclin D1 and v-myc avian myelocytomatosis viral oncogene homolog. Furthermore, [beta]-catenin was silenced by small interference RNA or overexpressed in CN cells, and the effect on cell proliferation was examined. The results indicated that silencing of [beta]-catenin enhanced the inhibitory effect of oridonin on cell growth, whereas the overexpression of [beta]-catenin attenuated this effect. These data indicated that oridonin inhibited proliferation and induced apoptosis to exert its antitumor activity in CN cells by repressing Wnt/[beta]-catenin signaling. Therefore, the present study suggested that oridonin might be an effective adjuvant agent, and that the Wnt/[beta]-catenin signaling pathway may be a potent target for the therapy in CN.