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Article: Downregulation of thymidylate synthase with arsenic trioxide in lung adenocarcinoma

TitleDownregulation of thymidylate synthase with arsenic trioxide in lung adenocarcinoma
Authors
Issue Date2014
Citation
International Journal of Oncology, 2014, v. 44, p. 2093-2102 How to Cite?
AbstractThymidylate synthase (TYMS) is an important chemotherapeutic target in non-small cell lung cancer (NSCLC). Arsenic trioxide (ATO) has been shown to suppress TYMS in a colonic cancer model. We examined the effects of TYMS suppression by ATO in lung adenocarcinoma. A panel of 4 lung adenocarcinoma cell lines was used to determine the effects of ATO treatment on cell viability, TYMS expression (protein and mRNA), E2F1 protein expression and TYMS activity. TYMS knockdown and overexpression were performed. Tumor growth inhibition in vivo was studied using a nude mouse xenograft model. ATO showed antiproliferative effects with clinically achievable concentrations (around 1.1-6.9 µM) in 4 lung adenocarcinoma cell lines. Downregulation of TYMS protein and mRNA expression, reduced TYMS activity, and suppressed E2F1 expression were demonstrated in lung adenocarcinoma with ATO. Cell viability was reduced by 15-50% with TYMS knockdown. Overexpression of TYMS led to a 2.7-fold increase in IC50 value with ATO treatment in H358 cells, but not in H23 cells. Using a xenograft model with H358 cell line, relative tumor volume was reduced to 44% that of the control following 8 days of treatment with 7.5 mg/kg ATO, and associated with significant downregulation of TYMS protein expression. In conclusion, ATO has potent in vitro and in vivo activity in lung adenocarcinoma, and is partially mediated by transcriptional downregulation of TYMS.
Persistent Identifierhttp://hdl.handle.net/10722/198037
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLam, SKen_US
dc.contributor.authorMak, JCWen_US
dc.contributor.authorZHENG, Cen_US
dc.contributor.authorLI, Yen_US
dc.contributor.authorKwong, YLen_US
dc.contributor.authorHo, JCMen_US
dc.date.accessioned2014-06-25T02:42:05Z-
dc.date.available2014-06-25T02:42:05Z-
dc.date.issued2014en_US
dc.identifier.citationInternational Journal of Oncology, 2014, v. 44, p. 2093-2102en_US
dc.identifier.urihttp://hdl.handle.net/10722/198037-
dc.description.abstractThymidylate synthase (TYMS) is an important chemotherapeutic target in non-small cell lung cancer (NSCLC). Arsenic trioxide (ATO) has been shown to suppress TYMS in a colonic cancer model. We examined the effects of TYMS suppression by ATO in lung adenocarcinoma. A panel of 4 lung adenocarcinoma cell lines was used to determine the effects of ATO treatment on cell viability, TYMS expression (protein and mRNA), E2F1 protein expression and TYMS activity. TYMS knockdown and overexpression were performed. Tumor growth inhibition in vivo was studied using a nude mouse xenograft model. ATO showed antiproliferative effects with clinically achievable concentrations (around 1.1-6.9 µM) in 4 lung adenocarcinoma cell lines. Downregulation of TYMS protein and mRNA expression, reduced TYMS activity, and suppressed E2F1 expression were demonstrated in lung adenocarcinoma with ATO. Cell viability was reduced by 15-50% with TYMS knockdown. Overexpression of TYMS led to a 2.7-fold increase in IC50 value with ATO treatment in H358 cells, but not in H23 cells. Using a xenograft model with H358 cell line, relative tumor volume was reduced to 44% that of the control following 8 days of treatment with 7.5 mg/kg ATO, and associated with significant downregulation of TYMS protein expression. In conclusion, ATO has potent in vitro and in vivo activity in lung adenocarcinoma, and is partially mediated by transcriptional downregulation of TYMS.en_US
dc.languageengen_US
dc.relation.ispartofInternational Journal of Oncologyen_US
dc.titleDownregulation of thymidylate synthase with arsenic trioxide in lung adenocarcinomaen_US
dc.typeArticleen_US
dc.identifier.emailLam, SK: sklam77@hku.hken_US
dc.identifier.emailMak, JCW: judithmak@hku.hken_US
dc.identifier.emailKwong, YL: ylkwong@hku.hken_US
dc.identifier.emailHo, JCM: jhocm@hku.hken_US
dc.identifier.authorityMak, JCW=rp00352en_US
dc.identifier.authorityKwong, YL=rp00358en_US
dc.identifier.authorityHo, JCM=rp00258en_US
dc.identifier.doi10.3892/ijo.2014.2364en_US
dc.identifier.pmid24691991-
dc.identifier.hkuros229169en_US
dc.identifier.volume44en_US
dc.identifier.spage2093en_US
dc.identifier.epage2102en_US
dc.identifier.isiWOS:000338694200034-

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