کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10753531 | 1050344 | 2015 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of MEK/ERK activation attenuates autophagy and potentiates pemetrexed-induced activity against HepG2 hepatocellular carcinoma cells
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کلمات کلیدی
LC-3mitogen-activated protein kinase/ERK kinase3-MAGFPERK3-methyladenine - 3-متیل آدنینHCC - HCCAutophagy - اتوفاژیBaf A1 - بافت A1bafilomycin A1 - بافیلومایسین A1Enzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاChemo-sensitization - حساسیت شیمیایی شیمیاییlight chain 3 - زنجیره سبک 3MEK - مجاهدین خلقGreen fluorescence protein - پروتئین فلورسانس سبزPemetrexed - پمترکسید، آلیمتاHepatocellular carcinoma (HCC) - کارسینوم سلولهای خونی (HCC)Hepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)Chloroquine - کلروکین extracellular-signal-regulated kinase - کیناز تنظیم شده خارج سلولی سیگنال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Identification of efficient chemo-therapeutic/chemo-preventive agents for treatment of hepatocellular carcinoma (HCC) is important. In this study, we examined the activity of pemetrexed, an anti-folate chemotherapy drug, against HepG2 human HCC cells. Pemetrexed treatment in vitro exerted weak but significant cytotoxic activity against HepG2 cells. When analyzing the possible pemetrexed-resistance factors, we indentified that pemetrexed treatment in HepG2 cells induced cyto-protective autophagy activation, evidenced by GFP-light chain 3B (LC3B) puncta formation, p62 downregulation and Beclin-1/LC3B-II upregulation. Correspondingly, autophagy inhibitors, including bafliomycin A1, 3-methyladenine and chloroquine, enhanced pemetrexed-induced cytotoxicity against HepG2 cells. Further, RNAi-mediated knockdown of Beclin-1 in HepG2 cells also increased pemetrexed sensitivity. Pemetrexed activated MEK (mitogen-activated protein kinase/ERK kinase)/ERK (extracellular-signal-regulated kinase) signaling in HepG2 cells, which was required for autophagy induction. Pharmacological inhibition of MEK/ERK activation attenuated pemetrexed-induced autophagy, enhanced HepG2 cell death and apoptosis. In summary, pemetrexed activates MEK/ERK-dependent cyto-protective autophagy, and inhibition of this pathway potentiates pemetrexed's activity in HepG2 cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 456, Issue 1, 2 January 2015, Pages 86-91
Journal: Biochemical and Biophysical Research Communications - Volume 456, Issue 1, 2 January 2015, Pages 86-91
نویسندگان
Tong Yongxi, Huang Haijun, Pan Hongying,