کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10899648 | 1084399 | 2014 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sorafenib overcomes the chemoresistance in HBx-expressing hepatocellular carcinoma cells through down-regulation of HBx protein stability and suppresses HBV gene expression
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کلمات کلیدی
zVAD-fmkMMPHepatitis B virus Xnecrostatin-1HBx proteinIFNαHBxPARPBAF3-MA3-methyladenine - 3-متیل آدنینHCC - HCCNec-1 - NEC-1AIF - آیفونinterferon alpha - اینترفرون آلفاbafilomycin A1 - بافیلومایسین A1Apoptosis - خزان یاختهایSorafenib - سورفانیبapoptosis-inducing factor - عامل القاء آپوپتوزHBV - هپاتیت بhepatitis B virus - ویروس هپاتیت بیMitochondrial membrane potential - پتانسیل غشای میتوکندریpoly (ADP-ribose) polymerase - پلی (ADP-ribose) پلیمرازHepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)Chloroquine - کلروکین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Sorafenib overcomes the chemoresistance in HBx-expressing hepatocellular carcinoma cells through down-regulation of HBx protein stability and suppresses HBV gene expression Sorafenib overcomes the chemoresistance in HBx-expressing hepatocellular carcinoma cells through down-regulation of HBx protein stability and suppresses HBV gene expression](/preview/png/10899648.png)
چکیده انگلیسی
Previous studies have revealed that HBx expression has anti-apoptotic effects, resulting in increased drug resistance in HCC cells. Thus, we examined if sorafenib efficiently induces apoptosis in HBx-overexpressing HCC cells. Noticeably, sorafenib efficiently induced apoptosis, even in HBx-expressing HepG2 cells, indicating that the HBx protein does not attenuate sorafenib-induced apoptosis. We next investigated if sorafenib modulates autophagy, allowing HCC cells to overcome the chemoresistance conferred by the HBx protein. Although autophagy plays a cytoprotective role against sorafenib-induced lethality, sorafenib was effective irrespective of HBx protein overexpression. We next examined if sorafenib exerts its cytotoxic effect via direct effects on the HBx protein. Importantly, sorafenib decreased HBx protein stability through a proteasome-dependent degradation pathway. Moreover, sorafenib decreased HBV gene expression and viral promoter activity. Taken together, sorafenib efficiently induces apoptotic cell death in HBx-expressing HCC cells via the downregulation of the HBx protein, a key factor in the anti-cancer drug resistance observed in HBV-induced HCC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 355, Issue 1, 1 December 2014, Pages 61-69
Journal: Cancer Letters - Volume 355, Issue 1, 1 December 2014, Pages 61-69
نویسندگان
Hye Young Kim, Hye Uk Jung, Seung Hee Yoo, Ki Soo Yoo, JaeHun Cheong, Bong Soo Park, Il Yun, Young Hyun Yoo,