کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8434871 | 1546652 | 2018 | 34 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Accumulating evidence has implicated the aberrant regulation of histone deacetylases (HDACs) as a nexus for multiple cancer hallmarks and in mediating tumor adaptation and resistance to genotoxic chemotherapy, suggesting a rational pairing of HDAC inhibitors with DNA damaging chemotherapeutic agents in the treatment of human malignancies. Here we report that panobinostat (LBH589), a potent pan-HDAC inhibitor, effectively curbed the proliferation of non-small cell lung cancer (NSCLC) cell lines A549, Calu-1, H226, H460, H838 and SKMES-1 at IC50 concentrations between 4 and 31â¯nmol/L via pleiotropic mechanisms, including crosstalk with EGFR signal transduction cascades. Combination therapy with carboplatin elicited rapid tumor cell kill and effectively restrained anchorage-independent clonogenic survival to a considerably greater extent over either monotherapy. The administration of carboplatin and panobinostat at clinically relevant doses to NOD-SCID xenograft mice drastically stalled disease progression by 92% as compared with negative control (Pâ¯=â¯.0026), which was greater than the 28% and 54% achieved with either carboplatin (Pâ¯=â¯.220) or panobinostat (Pâ¯=â¯.017) alone. These data demonstrate that panobinostat has strong anti-NSCLC activity and chemosensitizes tumors to carboplatin, thus justifying further evaluation of this combination approach in clinical trials.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 417, 28 March 2018, Pages 152-160
Journal: Cancer Letters - Volume 417, 28 March 2018, Pages 152-160
نویسندگان
Lingzhi Wang, Nicholas Li-Xun Syn, Vinod Vijay Subhash, Yijia Any, Win Lwin Thuya, Esther Sok Hwee Cheow, Liren Kong, Fenggang Yu, Praveen C. Peethala, Andrea Li-Ann Wong, Hirpara J. Laljibhai, Arunachalam Chinnathambi, Pei Shi Ong, Paul Chi-Lui Ho,