Department of Otolaryngology, The First Affiliated Hospital, Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, Shaanxi, China.
Department of Nuclear Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, Shaanxi, China.
Biochem Biophys Res Commun. 2019 Jun 11;513(4):846-851. doi: 10.1016/j.bbrc.2019.04.075. Epub 2019 Apr 16.
Tetrandrine (TET), a bis-benzylisoquinoline alkaloid, shows cytotoxicity against several different types of tumors. However, the mechanism by which TET exerts its anti-cancer capabilities remains unclear. In this study, we confirmed that TET inhibits proliferation and induces apoptosis in neuroblastoma (NB) in vitro and in vivo. Moreover, we revealed that the anti-cancer ability of TET is associated with a decreased expression of anti-apoptotic Bcl-2. Importantly, we demonstrated that the Hippo/YAP pathway is involved in down-regulating of Bcl-2. Notably, YAP overexpression promoted proliferation and suppressed apoptosis, even partially reversed TET-induced effects in NB cells. Our findings support the prospect that TET could be a potential therapeutic agent for NB, and suggest that targeting the Hippo/YAP pathway may represent a valuable approach to NB treatment.
汉防己甲素(TET)是一种双苄基异喹啉生物碱,对多种不同类型的肿瘤具有细胞毒性。然而,TET 发挥抗癌作用的机制尚不清楚。在本研究中,我们证实 TET 在体外和体内均能抑制神经母细胞瘤(NB)的增殖并诱导其凋亡。此外,我们揭示了 TET 的抗癌能力与抗凋亡 Bcl-2 表达降低有关。重要的是,我们证明 Hippo/YAP 通路参与下调 Bcl-2。值得注意的是,YAP 过表达促进增殖并抑制凋亡,甚至部分逆转了 TET 对 NB 细胞的诱导作用。我们的研究结果支持 TET 可能成为 NB 的一种潜在治疗药物的观点,并表明靶向 Hippo/YAP 通路可能是治疗 NB 的一种有价值的方法。