کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8292370 | 1536730 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Aspirin restores ABT-737-mediated apoptosis in human renal carcinoma cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monotherapy of renal cell carcinoma (RCC) are inconsistent across studies. ABT-737, an BH3 mimetic inhibitor, is also a promising antitumor drug. Cancer cells including those from RCC, that have high levels of Mcl-1, are refractory to ABT-737-induced apoptosis. We here investigated how aspirin treatment modulates the ABT-737-induced apoptosis. Using the in vitro model of human 786-O cells, we showed that aspirin had sensitized cells to ABT-737 induced apoptosis. Such aspirin-induced changes of ABT-737 resistance was accompanied by a host of biochemical events like protein phosphatase 2A (PP2A) activation, AKT dephosphorylation, Mcl-1/FLICE inhibiting protein (FLIP)/XIAP downregulation, and Bax mitochondrial redistribution. The PP2A inhibitor, okadaic acid, was able to reverse the apirin-induced apoptotic changes. Apart from the aspirin treatment, Mcl-1 silencing also rendered cells vulnerable to ABT-737 induced apoptosis. Since PP2A, Akt, and Mcl-1 play critical roles in RCC malignancy and treatment resistance, our present study showed that aspirin, an alternative adjuvant agent, had recalled ABT-737 sensitivity in the RCC cells through processes involving the PP2A/Akt/Mcl-1 axis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 502, Issue 2, 12 July 2018, Pages 187-193
Journal: Biochemical and Biophysical Research Communications - Volume 502, Issue 2, 12 July 2018, Pages 187-193
نویسندگان
Yen-Chuan Ou, Jian-Ri Li, Jiaan-Der Wang, Wen-Ying Chen, Yu-Hsiang Kuan, Ching-Ping Yang, Su-Lan Liao, Hsi-Chi Lu, Chun-Jung Chen,