Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Br J Cancer. 2012 Feb 28;106(5):876-82. doi: 10.1038/bjc.2012.36. Epub 2012 Feb 14.
The mammalian target of rapamycin (mTOR) protein is important for cellular growth and homeostasis. The presence and prognostic significance of inappropriate mTOR activation have been reported for several cancers. Mammalian target of rapamycin inhibitors, such as everolimus (RAD001), are in development and show promise as anti-cancer drugs; however, the therapeutic effect of everolimus on oesophageal squamous cell carcinoma (OSCC) remains unknown.
Phosphorylation of mTOR (p-mTOR) was evaluated in 167 resected OSCC tumours and 5 OSCC cell lines. The effects of everolimus on the OSCC cell lines TE4 and TE11 in vitro and alone or in combination with cisplatin on tumour growth in vivo were evaluated.
Mammalian target of rapamycin phosphorylation was detected in 116 tumours (69.5%) and all the 5 OSCC cell lines. Everolimus suppressed p-mTOR downstream pathways, inhibited proliferation and invasion, and induced apoptosis in both TE4 and TE11 cells. In a mouse xenograft model established with TE4 and TE11 cells, everolimus alone or in combination with cisplatin inhibited tumour growth.
The mTOR pathway was aberrantly activated in most OSCC tumours. Everolimus had a therapeutic effect both as a single agent and in combination with cisplatin. Everolimus could be a useful anti-cancer drug for patients with OSCC.
哺乳动物雷帕霉素靶蛋白（mTOR）对于细胞生长和内稳态很重要。已经报道了几种癌症中存在不当的 mTOR 激活及其预后意义。哺乳动物雷帕霉素靶蛋白抑制剂，如依维莫司（RAD001），正在开发中，并有望成为抗癌药物；然而，依维莫司对食管鳞状细胞癌（OSCC）的治疗效果尚不清楚。
在 167 例切除的 OSCC 肿瘤和 5 种 OSCC 细胞系中评估 mTOR 的磷酸化（p-mTOR）。评估依维莫司对体外 TE4 和 TE11 两种 OSCC 细胞系以及单独或联合顺铂对体内肿瘤生长的影响。
在 116 个肿瘤（69.5%）和所有 5 种 OSCC 细胞系中检测到 mTOR 磷酸化。依维莫司抑制了 p-mTOR 下游途径，抑制了增殖和侵袭，并诱导了 TE4 和 TE11 细胞的凋亡。在 TE4 和 TE11 细胞建立的小鼠异种移植模型中，依维莫司单独或联合顺铂抑制肿瘤生长。
大多数 OSCC 肿瘤中 mTOR 途径异常激活。依维莫司作为单一药物或联合顺铂均具有治疗作用。依维莫司可能是治疗 OSCC 患者的有用抗癌药物。
