Masitinib as a chemosensitizer of canine tumor cell lines: A proof of concept study

• Published in: The veterinary journal (1997) Vol. 191; no. 1; pp. 131 - 134
• Main Authors: Thamm, D.H., Rose, B., Kow, K., Humbert, M., Mansfield, C.D., Moussy, A., Hermine, O., Dubreuil, P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 2012
• Subjects: Animals; Antineoplastic Agents - pharmacology; Cancer; carcinoma; Cell Line, Tumor - drug effects; chemosensitization; Chemosensitizer; Chemotherapy; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Dog Diseases - drug therapy; Dog Diseases - pathology; Dogs; doxorubicin; Doxorubicin - administration & dosage; Drug Synergism; growth retardation; Inhibitory Concentration 50; Masitinib; osteosarcoma; pancreatic neoplasms; Protein Kinase Inhibitors - pharmacology; Sarcoma - drug therapy; Sarcoma - pathology; Sarcoma - veterinary; Thiazoles - pharmacology; vinblastine; Vinblastine - administration & dosage; Chemotherapy; Chemosensitizer; Masitinib; Dogs; Cancer
• ISSN: 1090-0233; 1532-2971
• DOI: 10.1016/j.tvjl.2011.01.001

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.