Liang Jingyan, Wang Weiguang, Wei Lifu, Gao Shan, Wang Yingge
Department of Anatomy, College of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
The Research Center for Vascular Biology, College of Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
Oncol Lett. 2018 Sep;16(3):3333-3340. doi: 10.3892/ol.2018.8977. Epub 2018 Jun 18.
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/β-catenin signaling pathway was examined. Western blot analysis indicated that oridonin markedly decreased the expression of β-catenin, cyclin D1 and v-myc avian myelocytomatosis viral oncogene homolog. Furthermore, β-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 β-catenin enhanced the inhibitory effect of oridonin on cell growth, whereas the overexpression of β-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/β-catenin signaling. Therefore, the present study suggested that oridonin might be an effective adjuvant agent, and that the Wnt/β-catenin signaling pathway may be a potent target for the therapy in CN.
中枢神经细胞瘤(CN)是一种发生于年轻成年人中枢神经系统的罕见的脑室周围肿瘤。通常情况下,CN患者预后良好,但在某些病例中,临床病程更为凶险。因此,研究有效的治疗方法至关重要。冬凌草甲素因其抗肿瘤活性而受到关注。然而,冬凌草甲素在肿瘤发生和进展中的作用仍不清楚。本研究检测了冬凌草甲素对CN细胞的抗肿瘤作用,并探讨了其潜在的分子机制。MTT法表明,冬凌草甲素处理能够显著抑制CN细胞的增殖。膜联蛋白V-异硫氰酸荧光素/碘化丙啶检测和蛋白质印迹分析表明,冬凌草甲素能够诱导细胞凋亡,并通过下调抗凋亡蛋白B细胞淋巴瘤-2(Bcl-2)和上调促凋亡蛋白Bcl-2样蛋白4、裂解的半胱天冬酶-3和裂解的聚(ADP-核糖)聚合酶1来改变凋亡相关蛋白的表达。随后,检测了Wnt/β-连环蛋白信号通路。蛋白质印迹分析表明,冬凌草甲素显著降低了β-连环蛋白、细胞周期蛋白D1和v-myc禽骨髓细胞瘤病毒癌基因同源物的表达。此外,通过小干扰RNA使β-连环蛋白沉默或在CN细胞中过表达,并检测其对细胞增殖的影响。结果表明,β-连环蛋白沉默增强了冬凌草甲素对细胞生长的抑制作用,而β-连环蛋白过表达则减弱了这种作用。这些数据表明,冬凌草甲素通过抑制Wnt/β-连环蛋白信号通路来抑制增殖并诱导凋亡,从而在CN细胞中发挥其抗肿瘤活性。因此,本研究表明,冬凌草甲素可能是一种有效的辅助药物,并且Wnt/β-连环蛋白信号通路可能是CN治疗的一个有效靶点。