کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5525489 | 1546671 | 2017 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
SVCT-2 determines the sensitivity to ascorbate-induced cell death in cholangiocarcinoma cell lines and patient derived xenografts
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کلمات کلیدی
AMPKS6KPBShistone 2Axsodium-dependent vitamin C transporterSVCTNACH2AXN-acetyl-l-cysteineHIFPDXp70 ribosomal S6 kinase - P6O سینوسی سدیم ریبوزومیROS - ROSPatient-derived xenografts - xenografts مشتق شده از بیمارAscorbic acid - آسکوربیک اسیدcombination index - شاخص ترکیبیHypoxia-inducible factor - فاکتور القاء کننده هیپوکسیPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریCholangiocarcinoma - کلانژیوکارسینومایReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (l-ascorbic acid, ascorbate) in several types of cancer. However, the effect of l-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo. Intriguingly, sodium-dependent vitamin C transporter 2 (SVCT-2) expression was inversely correlated with IC50 values of AA. Knockdown of SVCT-2 dramatically alleviated DNA damage, ATP depletion, and inhibition of mTOR pathway induced by AA. Furthermore, SVCT-2 knockdown endowed CC cells with the resistance to AA treatment. Finally, the inhibitory effects of AA were further confirmed in patient-derived CC xenograft models. Thus, our results unravel therapeutic potential of AA alone or in combination with cisplatin for CC. SVCT2 expression level may serve as a positive outcome predictor for AA treatment in CC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 398, 10 July 2017, Pages 1-11
Journal: Cancer Letters - Volume 398, 10 July 2017, Pages 1-11
نویسندگان
Changzheng Wang, Hongwei Lv, Wen Yang, Ting Li, Tian Fang, Guishuai Lv, Qin Han, Liwei Dong, Tianyi Jiang, Beige Jiang, Guangshun Yang, Hongyang Wang,