Evaluation of the drug sensitivity and expression of 16 drug resistance-related genes in canine histiocytic sarcoma cell lines

Canine histiocytic sarcoma (HS) is an aggressive tumor type originating from histiocyticcell lineages. This disease is characterized by poor response to chemotherapy and shortsurvival time. Therefore, it is of critical importance to identify and develop effectiveantitumor drugs against HS. The objectives of this study were to examine the drugsensitivities of 10 antitumor drugs. Using a real-time RT-PCR system, the mRNA expressionlevels of 16 genes related to drug resistance in 4 canine HS cell lines established fromdogs 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 microtubuleinhibitors (vincristine, vinblastine and paclitaxel), comparable to those in the canineB-cell lymphoma cell line. Moreover, it was shown that P-gp in the HS cell lines used inthis study did not have enough function to efflux its substrate. Sensitivities tomelphalan, nimustine, methotrexate, cytarabine, doxorubicin and etoposide were lower inthe 4 HS cell lines than in the 2 canine lymphoma cell lines. The data obtained in thisstudy using cultured cell lines could prove helpful in the developing of advanced andeffective chemotherapies for treating dogs that are suffering from HS.