title: Masitinib as a chemosensitizer of canine tumor cell lines: a proof of concept study.
abstract: Masitinib, a selective tyrosine kinase inhibitor, has previously been shown to enhance the antiproliferative effects of gemcitabine in human pancreatic cancer, demonstrating potential as a chemosensitizer. This exploratory study investigated the ability of masitinib to sensitize various canine cancer cell lines to doxorubicin, vinblastine, and gemcitabine. Masitinib strongly sensitized histiocytic sarcoma cells to vinblastine (>70-fold reduction in IC(50) at 5 μM masitinib), as well as osteosarcoma and mammary carcinoma cells to gemcitabine (>70-fold reduction at 5-10 μM). In addition, several cell lines were sensitized to doxorubicin (2-10-fold reduction at 10 μM). These data establish proof-of-concept that masitinib in combination with chemotherapeutic agents can generate synergistic growth inhibition in various canine cancers, possibly through chemosensitization. The findings justify further investigation into those combinations that may potentially yield therapeutic benefit.
authors.affiliation: The Animal Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523-1620, USA. dthamm@colostate.edu
authors.forename: D H
authors.initials: DH
authors.lastname: Thamm
authors.forename: B
authors.initials: B
authors.lastname: Rose
authors.forename: K
authors.initials: K
authors.lastname: Kow
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: C D
authors.initials: CD
authors.lastname: Mansfield
authors.forename: A
authors.initials: A
authors.lastname: Moussy
authors.forename: O
authors.initials: O
authors.lastname: Hermine
authors.forename: P
authors.initials: P
authors.lastname: Dubreuil
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D045744:Cell Line, Tumor / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D020128:Inhibitory Concentration 50; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D013844:Thiazoles / Q000494:pharmacology; D014747:Vinblastine / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; D003841:Deoxycytidine; D014747:Vinblastine; D004317:Doxorubicin; C526575:masitinib; D000093542:Gemcitabine