کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2116325 1084835 2013 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Potent antitumoral effects of targeted promoter-driven oncolytic adenovirus armed with Dm-dNK for breast cancer in vitro and in vivo
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Potent antitumoral effects of targeted promoter-driven oncolytic adenovirus armed with Dm-dNK for breast cancer in vitro and in vivo
چکیده انگلیسی

Currently, no curative treatments are available for late-stage metastatic or recurrent breast cancer, because the cancer tolerates both chemotherapy and endocrine therapy. In this study, we investigated the feasibility of a dual-regulated oncolytic adenoviral vector with a novel suicide gene to treat breast cancer. Following targeted gene virotherapy of conditionally replicating adenoviruses (CRAds), the novel suicide gene of multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-DNK) was inserted into the double-regulated oncolytic adenovirus SG500 to ensure more safety and enhanced antitumor activity against breast cancer both in vitro and in vivo. Selective replication, cell-killing efficacy, and cytotoxicity, combined with chemotherapeutics were investigated in several breast cell lines (MDA-MB-231 and MCF-7), normal cells (WI-38 and MRC-5), and human (MDA-MB-231) tumor models in vivo. The double-regulated SG500-dNK had high cell-killing activity in breast cancer. Replication was similar to wild-type in breast cells and was attenuated in normal cells. SG500-dNK combined with the chemotherapeutics (E)-5-(2-bromovinyl)-2′-deoxyuridine (Bvdu) and 2′,2′-difluoro-deoxycytidine (dFdC) resulted in synergistically enhanced cell killing and greatly improved antitumor efficacy in vitro or in breast xenografts in vivo. These data suggest that the novel oncolytic variant SG500-dNK is a promising candidate for targeting breast tumors specifically when combined with chemotherapeutics.


► The double-regulated SG500-dNK had high cell-killing activity in breast cancer.
► Replication in cancer cells and attenuated in normal cells.
► SG500-dNK/chemotherapeutics showed enhanced cell killing in vitro & in vivo.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 328, Issue 1, 1 January 2013, Pages 95–103
نویسندگان
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