Differential effects of peroxisome proliferator-activated receptor agonists on doxorubicinresistant human myelogenous leukemia (K562/DOX) cells

Differential effects of peroxisome proliferator-activated receptor agonists on doxorubicinresistant human myelogenous leukemia (K562/DOX) cells


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نویسندگان: بهمن یوسفی , نصرت اله ضرغامی , ناصر صمدی , بهزاد برادران , وحید شفیعی ایران نژاد

کلمات کلیدی: PPAR, multidrug resistance, P-glycoprotein, chronic myeloid leukemia, doxorubicin, cardiotoxicity

نشریه: 55091 , 61 , 8 , 2016

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نویسنده ثبت کننده مقاله ناصر صمدی
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه مرکز تحقیقات ایمونولوژی
کد مقاله 57362
عنوان فارسی مقاله Differential effects of peroxisome proliferator-activated receptor agonists on doxorubicinresistant human myelogenous leukemia (K562/DOX) cells
عنوان لاتین مقاله Differential effects of peroxisome proliferator-activated receptor agonists on doxorubicinresistant human myelogenous leukemia (K562/DOX) cells
ناشر 8
آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ بلی
عنوان نشریه (خارج از لیست فوق)
نوع مقاله Original Article
نحوه ایندکس شدن مقاله ایندکس شده سطح یک – ISI - Web of Science
آدرس لینک مقاله/ همایش در شبکه اینترنت http://www.cellmolbiol.com/

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P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in tumor cells is still a main obstacle for the chemotherapeutic treatment of cancers. Therefore, identification of safe and effective MDR reversing compounds with minimal adverse side effects is an important approach in the cancer treatment. Studies show that peroxisome proliferator-activated receptor (PPARs) ligands can inhibit cell growth in many cancers. Here, we investigated the effect of different PPAR agonists include fenofibrate, troglitazone and aleglitazar on doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells. The effects of doxorubicin (DOX) following treatment with PPAR agonists on cell viability were evaluated using MTT assay and the reversal fold (RF) values. Rhodamine123 (Rh123) assays were used to determine P-gp functioning. P-gp mRNA/protein expression was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis after incubation with troglitazone and aleglitazar. Our results showed that troglitazone and aleglitazar significantly enhanced the cytotoxicity of DOX and decreased the RF values in K562/DOX cells, however, no such results were found for fenofibrate. Troglitazone and aleglitazar significantly down regulated P-gp expression in K562/DOX cells; in addition, the present study revealed that aleglitazar elevated intracellular accumulation of Rh123in K562/DOX cells as short-term effects, which also contribute to the reversal of MDR. These findings show that troglitazone and especially aleglitazar exhibited potent effects in the reversal of P-gp-mediated MDR, suggesting that these compounds may be effective for combination therapy strategies and circumventing MDR in K562/DOX cells to other conventional chemotherapeutic drugs.

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نویسنده نفر چندم مقاله
بهمن یوسفیاول
نصرت اله ضرغامیهشتم
ناصر صمدیدوم
بهزاد برادرانسوم
وحید شفیعی ایران نژادپنجم

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Differential effects of peroxisome.pdf1394/12/03592006دانلود