title: Non-small cell lung carcinoma therapy using mTOR-siRNA.
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.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. hmatsu@yamanashi.ac.jp
authors.forename: Hirochika
authors.initials: H
authors.lastname: Matsubara
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakakibara
authors.forename: Tamo
authors.initials: T
authors.lastname: Kunimitsu
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Kaori
authors.initials: K
authors.lastname: Kato
authors.forename: Noboru
authors.initials: N
authors.lastname: Oyachi
authors.forename: Yoh
authors.initials: Y
authors.lastname: Dobashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002633:Chemotaxis; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases