title: Inhibition effect of Peg-IFNα-2b and Imatinib alone or combination on imatinib-resistant gastrointestinal stromal tumors cell lines.
abstract: To investigate the inhibition effect of polyethylene glycol interferon α-2b and imatinib alone or combination on imatinib-resistant GIST cell lines, and to explore the possible mechanism. Imatinib resistant GIST cell lines (GIST-R) were exposured to either Peg-IFNα-2b or imatinib alone or combination. The proliferative inhibition rates and the combination index (CI) values of GIST-R cells were detected by MTT assay. The apoptotic rates of GIST-R cells were detected by flow cytometry. The expression levels of phospho-mammalian target of rapamycin (p-mTOR), and Bcl-2 of GIST-R cells were analyzed by Western blot. GIST-R cells presents remarkable resistance to imatinib, and the resistance index (RI) were (P<0.05). And The proliferative inhibition rate and the apoptotic rate of GIST-R cells in combination of Peg-IFNα2b and Imatinib group were higher than those in Peg-IFNα-2b or imatinib alone group (P<0.05). The CI value of Peg-IFNα-2b and imatinib was less than each alone, which had a synergistic effect (CI=0.63). As compared with the control (GIST-R cells without any treatment), the expression levels of p-mTOR and Bcl-2 proteins of GIST-R cells in combination of Peg-IFNα-2b and imatinib group were decreased (P<0.01). The combination of Peg-IFNα-2b and imatinib generats a synergistic effect in GIST-R cells, and reversal of drug resistance. This effect may be related with apoptosis and down-regulation of the expression of p-mTOR.
authors.affiliation: Department of Minimally Invasive Surgery, The Second Xiangya Hospital of Central South University Changsha 421001, Hunan, China.
authors.forename: Lei-Yi
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Minimally Invasive Surgery, The Second Xiangya Hospital of Central South University Changsha 421001, Hunan, China.
authors.forename: Jiang-Sheng
authors.initials: JS
authors.lastname: Huang
authors.affiliation: Department of Minimally Invasive Surgery, The Second Xiangya Hospital of Central South University Changsha 421001, Hunan, China.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Pi
authors.affiliation: Department of Minimally Invasive Surgery, The Second Xiangya Hospital of Central South University Changsha 421001, Hunan, China.
authors.forename: Mei-Ying
authors.initials: MY
authors.lastname: Yu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011092:Polyethylene Glycols / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C000595707:BCL2 protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000068877:Imatinib Mesylate; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C417083:peginterferon alfa-2b
keywords: GIST; combination; drug resistance; imatinib; polyethylene glycol interferonα-2b; sensibilization