کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2580890 | 1130164 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sensitizing effect of 3-methyladenine on radiation-induced cytotoxicity in radio-resistant HepG2 cells in vitro and in tumor xenografts
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کلمات کلیدی
pifithrin-αPI3KGAPDHmTORAVOs3-MA3-methyladenine - 3-متیل آدنینHCC - HCCAcridine orange - آکاردین نارنجیAutophagy - اتوفاژیAcidic vesicular organelles - اندام های حسی اسیدیionizing radiation - تابش یوننده یا پرتوهای یونیزانRadio-resistance - رادیو مقاومتLiver cancer - سرطان کبدphosphoinositide 3-kinase - فسفینوزیتید 3-کینازmammalian target of rapamycin - هدف پستانداران رپامایسینPropidium iodide - پروتئین یدیدHepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)glyceraldehyde 3-phosphate dehydrogenase - گلیسرولیدید 3-فسفات دهیدروژناز
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Sensitizing effect of 3-methyladenine on radiation-induced cytotoxicity in radio-resistant HepG2 cells in vitro and in tumor xenografts Sensitizing effect of 3-methyladenine on radiation-induced cytotoxicity in radio-resistant HepG2 cells in vitro and in tumor xenografts](/preview/png/2580890.png)
چکیده انگلیسی
Many recent efforts have focused on targeting cell death pathways for discovering new cancer therapies. The relative resistance of liver cancer cells to ionizing radiation (IR) and chemotherapeutic agents due to autophagic response limits the available treatment options for this type of cancer. In this study, 3-methyladenine (3-MA), an autophagy inhibitor, was investigated for its potential to enhance radio-sensitivity under radio-resistant conditions both in vitro and in vivo. Hep3B and HepG2 cells were used to examine the radio-resistance of liver cancer cells. The results show that Hep3B cells respond to irradiation with increased apoptotic cell death and that HepG2 is radio-resistant due to the IR-induced autophagy, as verified by DNA fragmentation, electron microscopy, acidic vesicular organelle formation, and Western blot analysis. Application of IR with 3-MA to inhibit autophagy simultaneously suppressed the expression of LC3 and enhanced cell death. The tumor xenograft model in nude mice verified the synergistic cytotoxic effect of 3-MA and IR, which resulted in significant repression of tumor growth. The results demonstrate that IR-induced autophagy provides a self-protective mechanism against radiotherapy in HepG2 cells. In addition, 3-MA enhances the cytotoxicity of IR in cell models and suppresses tumor growth in animal models. Based on the results, application of 3-MA, or other autophagy inhibitors, could be used as an adjuvant for radiotherapy when radio-resistance develops as a result of autophagy response.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Chemico-Biological Interactions - Volume 192, Issue 3, 15 July 2011, Pages 201-208
Journal: Chemico-Biological Interactions - Volume 192, Issue 3, 15 July 2011, Pages 201-208
نویسندگان
Hsien-Chun Tseng, Wen-Shan Liu, Yeu-Sheng Tyan, Huei-Ching Chiang, Wu-Hsien Kuo, Fen-Pi Chou,