title: Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells.
abstract: In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29). Real time cell analysis (RTCA, Xcelligence system) was used to determine the effects on colorectal cancer cell proliferation. Apoptosis was assessed with annexin V staining and angiogenesis was determined with chorioallantoic membrane model. We found that motesanib alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Combination with DUP-697 increased the antiproliferative, antiangiogenic and apoptotic effects. Results of this study indicate that motesanib may be a good choice in treatment of colorectal tumors. In addition, the increased effects of combination of motesanib with DuP-697 raise the possibility of using lower doses of these drugs and therefore avoid/minimize the dose-dependent side effects generally observed.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Cumhuriyet University, Sivas, Turkey E-mail : nergizht@yahoo.com.
authors.forename: Tijen Temiz
authors.initials: TT
authors.lastname: Kaya
authors.forename: Ahmet
authors.initials: A
authors.lastname: Altun
authors.forename: Nergiz Hacer
authors.initials: NH
authors.lastname: Turgut
authors.forename: Hilmi
authors.initials: H
authors.lastname: Ataseven
authors.forename: Gokhan
authors.initials: G
authors.lastname: Koyluoglu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D009841:Oligonucleotides; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000008:administration & dosage
chemical_list: D020533:Angiogenesis Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D007211:Indoles; D009841:Oligonucleotides; D047428:Protein Kinase Inhibitors; D013876:Thiophenes; D009536:Niacinamide; C064874:DuP 697; D051546:Cyclooxygenase 2; C519562:imetelstat