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
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出版日期 | 2008-09-01 |
卷号 | 14期号:17页码:5519-5530 |
ISSN号 | 1078-0432 |
DOI | 10.1158/1078-0432.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 |
推荐引用方式 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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来源:中国科学院大学
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