کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5799012 1111784 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The proteasome inhibitor bortezomib inhibits the growth of canine malignant melanoma cells in vitro and in vivo
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم دامی و جانورشناسی
پیش نمایش صفحه اول مقاله
The proteasome inhibitor bortezomib inhibits the growth of canine malignant melanoma cells in vitro and in vivo
چکیده انگلیسی

Canine malignant melanomas are highly aggressive and fatal neoplasms. In the present report, 21 drugs that target specific signalling pathways were screened for their growth inhibitory activity on three canine malignant melanoma cell lines. The proteasome inhibitor bortezomib inhibited the growth of these cell lines. The growth inhibitory properties of bortezomib were then examined using nine canine malignant melanoma cell lines. Bortezomib demonstrated potent growth inhibitory activity in all cell lines with calculated IC50 values of 3.5-5.6 nM.Because suppression of the NF-κB pathway by preventing proteasomic degradation of IκB is an important mechanism of the anti-tumour activity of bortezomib, the activation status of and the effect of bortezomib on the NF-κB pathway were examined using a canine malignant melanoma cell line, CMM-1. The NF-κB pathway was constitutively activated in CMM-1 cells and bortezomib efficiently suppressed this activated pathway. Using a CMM-1 xenograft mouse model, bortezomib also significantly inhibited tumour growth via suppression of tumour cell proliferation.Collectively, these findings suggest that bortezomib has growth inhibitory activity against canine malignant melanomas potentially through suppression of the constitutively activated NF-κB pathway. Targeted therapy using bortezomib could therefore be beneficial in the management of canine malignant melanomas.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Veterinary Journal - Volume 198, Issue 3, December 2013, Pages 577-582
نویسندگان
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