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

Asada H, Tomiyasu H, Goto-Koshino Y, Fujino Y, Ohno K, Tsujimoto H - J. Vet. Med. Sci. (2015)

Bottom Line: Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS.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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Graphs illustrating the mRNA expression levels of (a)ABCB1,(b)ABCG2, (c)TP53,(d)p21waf1 and (e)MSH6. All datarepresent the mean ± SD of three independent experiments. *P<0.05(one-way ANOVA followed by Tukey’s post-hoc test).
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fig_002: Graphs illustrating the mRNA expression levels of (a)ABCB1,(b)ABCG2, (c)TP53,(d)p21waf1 and (e)MSH6. All datarepresent the mean ± SD of three independent experiments. *P<0.05(one-way ANOVA followed by Tukey’s post-hoc test).

Mentions: Quantitative analysis of mRNA by real-time RT-PCR: The expression levelsof 16 drug resistance genes are shown in “Supplementary file 5”. In addition, comparisons of5 genes showing the relative quantities that were significantly different between HS andlymphoma cell lines are illustrated in the graphs (Fig.2Fig. 2.


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

Asada H, Tomiyasu H, Goto-Koshino Y, Fujino Y, Ohno K, Tsujimoto H - J. Vet. Med. Sci. (2015)

Graphs illustrating the mRNA expression levels of (a)ABCB1,(b)ABCG2, (c)TP53,(d)p21waf1 and (e)MSH6. All datarepresent the mean ± SD of three independent experiments. *P<0.05(one-way ANOVA followed by Tukey’s post-hoc test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488404&req=5

fig_002: Graphs illustrating the mRNA expression levels of (a)ABCB1,(b)ABCG2, (c)TP53,(d)p21waf1 and (e)MSH6. All datarepresent the mean ± SD of three independent experiments. *P<0.05(one-way ANOVA followed by Tukey’s post-hoc test).
Mentions: Quantitative analysis of mRNA by real-time RT-PCR: The expression levelsof 16 drug resistance genes are shown in “Supplementary file 5”. In addition, comparisons of5 genes showing the relative quantities that were significantly different between HS andlymphoma cell lines are illustrated in the graphs (Fig.2Fig. 2.

Bottom Line: Therefore, it is of critical importance to identify and develop effective antitumor drugs against HS.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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Science, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.

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.

No MeSH data available.


Related in: MedlinePlus