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Chinese Academy of Sciences Institutional Repositories Grid
Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action

文献类型:期刊论文

作者Hou, Junmei1,2; Wang, Disong3; Zhang, Ruiwen4,5,6; Wang, Hui1,2
刊名Clinical cancer research
出版日期2008-09-01
卷号14期号:17页码:5519-5530
ISSN号1078-0432
DOI10.1158/1078-0432.ccr-08-0197
通讯作者Wang, hui(huiwang@sibs.ac.cn)
英文摘要Purpose: art and its derivatives, clinically used antimalarial agents, have recently shown antitumor activities. however, the mechanisms underlying these activities remain unclear. this study was designed to determine their antitumor efficacy and underlying mechanisms of action in human hepatoma cells. experimental design: the in vitro cytotoxicities of art, dha, artemether, and artesunate were compared in human hepatoma cells, hepg2 (p53 wild-type), huh-7 and bel-7404 (p53 mutant), and hep3b (p53 null), and a normal human liver cell line, 7702. based on their activity and specificity, art and dha were further investigated for their in vitro and in vivo antitumor effects and their effects on the protein expression of genes associated with cell proliferation and apoptosis. results: art and dha exerted the greatest cytotoxicity to hepatoma cells but significantly lower cytotoxicity to normal liver cells. the compounds inhibited cell proliferation, induced g(1)-phase arrest, decreased the levels of cyclin d1, cyclin e, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and e2f1, and increased the levels of cip1/p21 and kip1/p27. they induced apoptosis, activated caspase-3, increased the bax/bcl-2 ratio and poly (adp-ribose) polymerase, and down-regulated mdm2. in mice bearing hepg2 and hep3b xenograft tumors, art and dha inhibited tumor growth and modulated tumor gene expression consistent with in vitro observations. dha increased the efficacy of the chemotherapeutic agent gemcitabine. conclusions: art and dha have significant anticancer effects against human hepatoma cells, regardless of p53 status, with minimal effects on normal cells, indicating that they are promising therapeutics for human hepatoma used alone or in combination with other therapies.
WOS关键词ADVANCED HEPATOCELLULAR-CARCINOMA ; ANTIMALARIAL ARTESUNATE ; ANTITUMOR-ACTIVITY ; CENTERED RADICALS ; CDK INHIBITORS ; CANCER-THERAPY ; BREAST-CANCER ; CELL-CYCLE ; PHASE-II ; APOPTOSIS
WOS研究方向Oncology
WOS类目Oncology
语种英语
WOS记录号WOS:000259166000025
出版者AMER ASSOC CANCER RESEARCH
URI标识http://www.irgrid.ac.cn/handle/1471x/2388498
专题中国科学院大学
通讯作者Wang, Hui
作者单位1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China
3.Commiss Shanghai Municipal, Dept Basic Res Sci & Technol, Shanghai, Peoples R China
4.Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL USA
5.Univ Alabama, Div Clin Pharmacol, Birmingham, AL USA
6.Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA
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GB/T 7714
Hou, Junmei,Wang, Disong,Zhang, Ruiwen,et al. Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action[J]. Clinical cancer research,2008,14(17):5519-5530.
APA Hou, Junmei,Wang, Disong,Zhang, Ruiwen,&Wang, Hui.(2008).Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action.Clinical cancer research,14(17),5519-5530.
MLA Hou, Junmei,et al."Experimental therapy of hepatoma with artemisinin and its derivatives: in vitro and in vivo activity, chemosensitization, and mechanisms of action".Clinical cancer research 14.17(2008):5519-5530.

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