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Int J Clin Exp Pathol 2012;5(2):119-125

Original Article
Non-small cell lung carcinoma therapy using mTOR-siRNA

Hirochika Matsubara, Kenji Sakakibara, Tamo Kunimitsu, Hiroyasu Matsuoka, Kaori Kato, Noboru Oyachi, Yoh Dobashi, Masahiko Matsumoto

Division of Cardiovascular Surgery, Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan; Department of
Pathology, Saitama Medical Center, Jichi Medical University, Saitama, Japan

Received December 15, 2011; accepted January 19, 2012; Epub February 12, 2012; Published February 28, 2012

Abstract: Molecular targeting agents play important roles in non-small-cell lung cancer (NSCLC) therapy. Published studies have investigated
new drugs categorized as molecular targeting agents that inhibit the mammalian target of rapamycin (mTOR). We focused on a small
interfering RNA (siRNA) that specifically inhibits mTOR and has fewer side effects. To evaluate the antitumor effects of the siRNA, cell
proliferation, apoptosis, and migration were assessed. In the study group, the siRNA was transfected into NSCLC cells. The number of cells
present after 6 days of culture was counted to determine changes in cell proliferation. The level of apoptosis was evaluated by the detection of
DNA-histone complexes in the cytoplasmic fraction using an absorption spectrometer. Changes in migration were evaluated by calculating the
number of cells that passed through a specific filter using a commercial chemotaxis assay kit. mTOR-siRNA transfection inhibited cell
proliferation as indicated by 37.3% (p = 0.034) decrease in the number of cells compared with the control cells. Analysis of the level of
apoptosis in NSCLC cells revealed 16.7% (p = 0.016) increase following mTOR-siRNA transfection, and mTOR-siRNA transfection significantly
inhibited cell migration by 39.2% (p = 0.0001). We confirmed that mTOR-siRNA induces apoptosis and inhibits the proliferation and migration
of NSCLC cells in vitro. Further studies using mTOR-siRNA may aid in the development of an alternative therapy that maximizes the
antineoplastic effect of mTOR inhibition.

Keywords: mTOR, siRNA, non-small-cell lung cancer

Address all correspondence to:
Dr. Hirochika Matsubara
Department of Surgery, Faculty of Medicine
University of Yamanashi, 1110 Shimokato
Chuou, Yamanashi 409-3898, Japan.
Tel: +81-55-273-9682; Fax: +81-55-273-6767
E-mail: hmatsu@yamanashi.ac.jp