کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10901507 | 1084703 | 2016 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of mitochondrial oxidation by PDK2 inhibition reverses cisplatin resistance in head and neck cancer
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کلمات کلیدی
DCAPDK2MTVHNCCDDPPARPDCF-DANACOXPHOS18F-fluorodeoxyglucose18F-FDGΔΨmN-acetyl-l-cysteine2′,7′-dichlorofluorescein diacetate - 2 '، 7'-dichlorofluorescein diacetateshort interfering RNA - RNA تداخل کوتاهROS - ROSsiRNA - siRNAPositron emission tomography - توموگرافی گسیل پوزیترونTUNEL - تونلMetabolic tumor volume - حجم تومور متابولیکDichloroacetate - دی کلرواساتاتHead and neck cancer - سرطانهای سر و گردنcisplatin - سیس پلاتینOxidative phosphorylation - فسفوریلاسیون اکسیداتیوterminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling - مارک نهایی با نام dUTP تخصیص داده شده توسط ترمینال deoxynucleotidyl transferase استSUV - ماشین شاسی بلندCisplatin resistance - مقاومت سیس پلاتینstandardized uptake value - مقدار جذب استاندارد شدهPET - پتMitochondrial membrane potential - پتانسیل غشای میتوکندریPoly(ADP-ribose) polymerase - پلیمر (ADP-ribose) پلیمرازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Activation of mitochondrial oxidation by PDK2 inhibition reverses cisplatin resistance in head and neck cancer Activation of mitochondrial oxidation by PDK2 inhibition reverses cisplatin resistance in head and neck cancer](/preview/png/10901507.png)
چکیده انگلیسی
Dichloroacetate (DCA), an orphan drug that promotes a shift from glycolysis to oxidative phosphorylation, has been repurposed for cancer therapy. The present study investigated whether DCA may overcome cisplatin resistance in head and neck cancer (HNC). Two cisplatin-resistant HNC cell lines (AMC-HN4R and -HN9R), their parental lines, and other human HNC lines were used. The effect of DCA, alone and in combination with cisplatin, was assessed by measuring cell cycle, viability, death, reactive oxygen species (ROS) production, mitochondrial membrane potential (ÎΨm), and protein expression in preclinical mouse tumor xenograft models. Increased glycolysis correlated with decreased sensitivity to cisplatin and was reduced by DCA. Cisplatin-resistant cells overexpressed pyruvate dehydrogenase kinase 2 (PDK2). DCA induced HNC cell death by decreasing ÎΨm and promoting mitochondrial ROS production. This effect was decreased by the antioxidant N-acetyl-l-cysteine or by inhibition of caspase-mediated apoptosis. Activation of mitochondrial glucose oxidation by DCA eventually activated downstream mitochondrial apoptotic signaling, leading to the death of chemoresistant cancer cells. Therefore, DCA significantly sensitized resistant HNC cells to cisplatin in vitro and in vivo. High glycolysis and PDK2 overexpression are closely linked to cisplatin resistance in HNC cells; the latter can be overcome by DCA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 371, Issue 1, 1 February 2016, Pages 20-29
Journal: Cancer Letters - Volume 371, Issue 1, 1 February 2016, Pages 20-29
نویسندگان
Jong-Lyel Roh, Jin Young Park, Eun Hye Kim, Hye Jin Jang, Minsu Kwon,