Temsirolimus诱导的自噬对腺样囊性癌的作用

目的：探讨Temsirolimus对腺样囊性癌ACC-M细胞株自噬水平的影响,以研究该药物诱导的自噬对腺样囊性癌细胞的作用。方法：通过细胞增殖实验研究Temsirolimus对ACC-M细胞增殖的影响;通过Western印迹检测实验组与对照组微管相关蛋白1轻链3（LC3）和Beclin1的表达差异;利用透射电镜观察ACC-M细胞中自噬体的形态及数量,采用SPSS15.0软件包对实验结果进行t检验。结果：Temsirolimus对ACC-M细胞具有明显的生长抑制作用,并呈现出剂量-效应关系;LC3和Beclin1在实验组细胞中表达水平高于对照组（P〈0.05）;透射电镜实验中,实验组细胞胞内自噬体及自噬溶酶体数量明显高于对照组（P〈0.01）。结论：Temsirolimus通过诱导ACC-M细胞自噬,产生了明显的抑制肿瘤细胞生长的作用,提示细胞自噬是Temsirolimus作用于唾液腺腺样囊性癌的重要抗肿瘤机制。

Temsirolimus,the mTOR inhibitor,induces autophagy in adenoid cystic carcinoma

PURPOSE： 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 the effect of temsirolimus on ACC-M cells, via induction of autophagy. METHODS： ACC-M cells were treated with temsirolimus in appropriate concentration, the cytotoxic activity of temsirolimus was determined by MTT assay; transmission electron microscopy（TEM） was used to observe autophagosomes in ACC-M cells; autophagy was reflected by the expression of LC3 and Beclin1. Data was expressed as mean±SEM of at least three independent experiments. Statistical comparisons between groups were performed using two-tailed Student＇s t test with SPSS 15.0 software package. RESULTS： MTT assay showed that the inhibition effect of temsirolimus assumed an obvious dose-response relationship on ACC-M cells; numerous autophagosomes were observed by transmission electron microscopy（TEM） in temsirolimus treatment groups; in addition,expression of LC3 and Beclin1 was significantly up-regulated by temsirolimus. CONCLUSIONS： The results suggest that temsirolimus could act as an mTOR inhibitor to induce autophagy in adenoid cystic carcinoma.