Mechanistic Target of Rapamycin Small Interfering RNA and Rapamycin Synergistically Inhibit Tumour Growth in a Mouse Xenograft Model of Human Oesophageal Carcinoma  

Oleh:

Sun, M.M. ; Zhang, M.Z. ; Chen, Y. ; Li, S.L. ; Sadikin-Susilo

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The Journal of International Medical Research vol. 40 no. 05 (Sep. 2012), page 1636-1643.
Topik: Ec1 Cells; Hypoxia Inducible Factor 1alpha; Mechanistic Target Of Rapamycin; Mouse Xenograft Model; Oesophageal Cancer; Rapamycin; Small Interfering Rna; Vascular Endothelial Growth Factor

Ketersediaan

Perpustakaan FK Nomor Panggil: J11.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

OBJECTIVES: To investigate the effect of mechanistic target of rapamycin (mTOR)-specific small interfering RNA (siRNA) and rapamycin on tumour size and levels of hypoxia inducible factor 1a(HIF-1a), vascular endothelial growth factor (VEGF) and mTOR proteins, and mTOR mRNA, in a mouse xenograft model of human oesophageal carcinoma. METHODS: Tumours were induced in BALB/c nude mice using the human oesophageal squamous cell carcinoma cell line, EC1, injected subcutaneously. Animals were divided into four treatment groups (n = 5 per group) after 7 days: control (phosphate buffered saline, daily intraperitoneal [i.p.] injection); 50 µg/kg rapamycin, daily i.p. injection; 3 µg/kg mTOR siRNA, daily i.p. injection; combined mTOR siRNA and rapamycin, daily i.p. injections. Tumour volume was measured 21 days after xenograft. Levels of mTOR, VEGF and HIF-1a were assessed via immunohisto chemistry and in situ hybridization. RESULTS: mTOR siRNA and/or rapamycin significantly decreased tumour volume and levels of HIF-1a, VEGF and mTOR protein, and mTOR mRNA. Combination treatment was significantly more effective than either treatment alone. CONCLUSIONS: mTOR siRNA and/or rapamycin inhibited the growth of oesophageal carcinoma in vivo. This may represent a novel and effective treatment strategy for oesophageal carcinoma.

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