title: Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines.
abstract: Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocytic cell lineages. This disease is characterized by poor response to chemotherapy and short survival time. Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS. The objectives of this study were to examine the drug sensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expression levels of 16 genes related to drug resistance in 4 canine HS cell lines established from dogs with disseminated HS were determined and compared to 2 canine lymphoma cell lines (B-cell and T-cell). These 4 canine HS cell lines showed sensitivities toward microtubule inhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canine B-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used in this study did not have enough function to efflux its substrate. Sensitivities to melphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower in the 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in this study using cultured cell lines could prove helpful in the developing of advanced and effective chemotherapies for treating dogs that are suffering from HS.
authors.affiliation: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Asada
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tomiyasu
authors.forename: Yuko
authors.initials: Y
authors.lastname: Goto-Koshino
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Fujino
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohno
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsujimoto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000494:pharmacology; D004283:Dog Diseases / Q000188:drug therapy* / Q000235:genetics*; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000662:veterinary*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor / Q000662:veterinary*; D005047:Etoposide / Q000494:pharmacology; D054747:Histiocytic Sarcoma / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D008558:Melphalan / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology; D015376:Nimustine / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D014747:Vinblastine / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003561:Cytarabine; D015376:Nimustine; D014750:Vincristine; D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D017239:Paclitaxel; D008558:Melphalan; D008727:Methotrexate