Liu Wenlei, Huang Shengyun, Chen Zhanwei, Wang Huachun, Wu Haiwei, Zhang Dongsheng
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
Pathol Res Pract. 2014 Nov;210(11):764-9. doi: 10.1016/j.prp.2014.03.008. Epub 2014 Mar 30.
Temsirolimus acts as a mammalian target of rapamycin (mTOR)-dependent autophagic inhibitor. In order to clarify its effects and mechanisms on human salivary adenoid cystic carcinoma (ACC), we examined whether temsirolimus induced autophagy as the mTOR inhibitor in ACC, both in vitro and in vivo. In this study, MTT assay showed that the inhibition effect of temsirolimus assumed an obvious dose-response relationship on ACC-M cells, and the 50% inhibitory concentration (IC(50)) approached 20 μmol/l; numerous autophagosomes were observed by the transmission electron microscopy (TEM) in temsirolimus treatment groups; notably, expression of LC3 and Beclin1 was significantly up-regulated by temsirolimus. More importantly, the xenograft model provided further evidence of temsirolimus-induced autophagy in vivo by inhibiting mTOR activation as well as up-regulation the expression of Beclin1. These results suggest that temsirolimus could act as an mTOR inhibitor to induce autophagy in adenoid cystic carcinoma both in vitro and in vivo.
替西罗莫司作为一种依赖雷帕霉素靶蛋白(mTOR)的自噬抑制剂。为了阐明其对人涎腺腺样囊性癌(ACC)的作用及其机制,我们在体外和体内研究了替西罗莫司作为ACC中的mTOR抑制剂是否诱导自噬。在本研究中,MTT试验表明,替西罗莫司对ACC-M细胞的抑制作用呈现明显的剂量反应关系,50%抑制浓度(IC50)接近20μmol/L;在替西罗莫司治疗组中通过透射电子显微镜(TEM)观察到大量自噬体;值得注意的是,替西罗莫司显著上调了LC3和Beclin1的表达。更重要的是,异种移植模型通过抑制mTOR激活以及上调Beclin1的表达,进一步证明了替西罗莫司在体内诱导自噬。这些结果表明,替西罗莫司可作为mTOR抑制剂在体外和体内诱导腺样囊性癌中的自噬。