کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2524665 | 1557959 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synergistic inhibition of sunitinib and ethaselen against human colorectal cancer cells proliferation
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کلمات کلیدی
Dose-reduction indexVEGFRsBBSKEDRISRBVEGFRTKITrxTrxRBcl-2/Bax - Bcl-2 / BaxROS - ROSthioredoxin reductase - تریودوکسین ردوکتازthioredoxin - تیرودوکسینSunitinib - سانیتینیبColorectal cancer - سرطان روده بزرگNSCLC - سرطان ریوی غیر سلول کوچکNon-small cell lung cancer - سرطان غیر سلول کوچک ریهsulforhodamine B - سولفوردامین بcytochrome c - سیتوکروم سیcombination index - شاخص ترکیبیTyrosine kinase inhibitor - مهار کننده تیروزین کینازCRC - کد افزونگی دورهای Reactive oxygen species - گونههای فعال اکسیژنVascular endothelial growth factor receptors - گیرنده های فاکتور رشد اندوتلیال عروقیplatelet-derived growth factor receptors - گیرنده های فاکتور رشد فلوتر
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
تومور شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Sunitinib, a multi-targeted tyrosine kinase inhibitor, has been widely used in the therapy of advanced renal cell cancer and imatinib-resistant gastrointestinal stromal tumors. However, little benefits could be obtained from sunitinib for patients with other types of solid tumors including colorectal cancer (CRC). Ethaselen (BBSKE), a specific thioredoxin reductase 1 inhibitor, has shown convincing anticancer effects both in vivo and in vitro. In this study, we explored the combinatory effect of sunitinib and BBSKE in human CRC cell lines LoVo, HT-29 and RKO. Cotreatment of BBSKE and sunitinib with the ratio of 2:1 for 24Â h displayed synergistic effect against CRC cells proliferation. Apoptosis analysis also revealed that combination treatment of BBSKE and sunitinib (2:1) for 24Â h induced higher apoptosis rate than either single treatment. The synergistic effect against LoVo cells proliferation may be explained by sharp reduction of Bcl-2/Bax protein expression ratio, decrease of pro-Caspase-3 protein expression along with significantly augmented Caspase-3 enzymatic activity, and release of cytochrome C from mitochondria to cytoplasm in the combination treatment group. The significant inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation might also account for the synergism in cotreatment group. In short, sunitinib plus BBSKE is perhaps a promising strategy for colorectal cancer therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomedicine & Pharmacotherapy - Volume 83, October 2016, Pages 212-220
Journal: Biomedicine & Pharmacotherapy - Volume 83, October 2016, Pages 212-220
نویسندگان
Xiaoqing Zheng, Yunhan Zhang, Lei Zhang, Wei Xu, Weiwei Ma, Ruoxuan Sun, Huihui Zeng,