Abstract:
:The aim of this study was to test whether long-term ethanol consumption confers therapeutic resistance to human liver cancer patients infected with hepatitis B virus (HBV). Chronic ethanol-treated cells were established by consecutively culturing a human hepatocellular carcinoma cell line, Hep 3B, which contains integrated HBV sequences, for 20-40 passages with or without 10 mM ethanol (designated as E20-E40 and C20-C40, respectively). Flow cytometry analysis demonstrated that a growth promoting effect of long-term ethanol treatment was induced in the E40 cells through preferential acceleration of S-phase in these cells. Lower protein expression levels of p16, p21/Cip1, and p27/Kip1 were detected in the ethanol-treated E40 cells. We further demonstrated that long-term ethanol-treated E40 cells develop drug resistance in response to mitomycin C (MMC) treatment (>8 microM). Immunoblot analysis revealed that caspase-8-mediated mitochondrial apoptotic signals (such as Bad) were inactivated in the MMC-resistant E40 cells. Immunoprecipitation experiments demonstrated that the sequestration of phosphorylated Bad (Ser-112) through its binding with 14-3-3 was detected more profoundly in the MMC-resistant E40 cells. Next, we examined the therapeutic efficacy of MMC (10 mg MMC/kg body weight, three times per week) in severe combined immunodeficient (SCID) mice bearing E40- and C40-xenografted tumors. Significant reductions (>3-fold) in tumor growth were detected in MMC-treated C40-xenografted mice. In vivo and in vitro studies demonstrated that AKT- and extracellular signal-regulated kinase (ERK)-mediated survival factors inhibited the Bad-induced mitochondrial apoptotic signals that were involved in E40 tumor cells and that conferred resistance to MMC.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Huang CS,Lee YR,Chen CS,Tu SH,Wang YJ,Lee CH,Chen LC,Chang HW,Chang CH,Chih-Ming S,Wu CH,Ho YSdoi
10.1002/mc.20648subject
Has Abstractpub_date
2010-08-01 00:00:00pages
728-38issue
8eissn
0899-1987issn
1098-2744journal_volume
49pub_type
杂志文章abstract::Development of chemoresistance in androgen-refractory prostate cancer cells is partly due to constitutive activation of Rel/NF-kappaB transcription factors that regulate several cell survival and anti-apoptotic genes. In this study we examined whether betulinic acid (BetA), a pentacyclic triterpene from the bark of wh...
journal_title:Molecular carcinogenesis
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更新日期:2008-12-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2005-07-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2018-11-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2008-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940110109
更新日期:1994-09-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20129
更新日期:2005-11-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22069
更新日期:2015-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199711)20:3<298::aid-mc6>3
更新日期:1997-11-01 00:00:00
abstract::2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a compound found in cooked meat, is a mammary gland carcinogen in female Sprague-Dawley rats. PhIP-induced rat mammary gland carcinomas were examined for mutations in several genes (exons) known to regulate cell growth and apoptosis, including p53 (4-8), p21(Waf1...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(200002)27:2<76::aid-mc3>3.
更新日期:2000-02-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20496
更新日期:2009-04-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940130209
更新日期:1995-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20017
更新日期:2004-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2001-10-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
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更新日期:2007-08-01 00:00:00
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更新日期:2015-10-01 00:00:00
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更新日期:2017-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-03-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:1999-06-01 00:00:00
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更新日期:2016-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-06-01 00:00:00
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更新日期:2013-08-01 00:00:00
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更新日期:2014-11-01 00:00:00
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更新日期:2007-01-01 00:00:00