Evaluation of the drug sensitivity and expression of 16 drug
resistance-related genes in canine histiocytic sarcoma cell lines |
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Authors: | Hajime ASADA Hirotaka TOMIYASU Yuko GOTO-KOSHINO Yasuhito FUJINO Koichi OHNO Hajime TSUJIMOTO |
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Institution: | 1)Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113–8657, Japan |
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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. |
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Keywords: | canine drug resistance histiocytic sarcoma microtubule inhibitors TP53 gene |
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