Aberrant activation of the mTOR pathway and anti-tumour effect of everolimus on oesophageal squamous cell carcinoma

被引：54

作者：

Hirashima, K. ^{[1
,2
]}

Baba, Y. ^{[1
,2
]}

Watanabe, M. ^{[1
]}

Karashima, R-I ^{[1
]}

Sato, N. ^{[1
]}

Imamura, Y. ^{[1
]}

Nagai, Y. ^{[1
]}

Hayashi, N. ^{[1
]}

Iyama, K-I ^{[2
]}

Baba, H. ^{[1
]}

机构：

[1] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto 8608556, Japan

[2] Kumamoto Univ Hosp, Dept Surg Pathol, Kumamoto 8608556, Japan

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 106卷 / 05期

关键词：

everolimus; RAD001; mTOR; oesophageal squamous cell carcinoma; proliferation; RAPAMYCIN INHIBITOR EVEROLIMUS; MAMMALIAN TARGET; PHASE-I; RAD001; EVEROLIMUS; SIGNALING PATHWAY; INDUCED APOPTOSIS; BREAST-CANCER; EXPRESSION; RATIONALE; RESISTANT;

D O I：

10.1038/bjc.2012.36

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. British Journal of Cancer (2012) 106, 876-882. doi:10.1038/bjc.2012.36 www.bjcancer.com Published online 14 February 2012 (C) 2012 Cancer Research UK

引用

页码：876 / 882

页数：7

共 46 条

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