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Conference Paper: mTOR inhibitor sensitizes chemo-cytotoxicity for hepatocellular carcinoma

TitlemTOR inhibitor sensitizes chemo-cytotoxicity for hepatocellular carcinoma
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research
Citation
The 97th Annual Meeting of the American Association for Cancer Research, Washington D.C. 1 - 5 April 2006. In Cancer Research, 2006, v. 66 n. 8 S, Abstract no. 1352 How to Cite?
AbstractObjective: Chemo-resistance is a major concern in the treatment of hepatocellular carcinoma (HCC). Several studies have demonstrated that inhibition of mammalian target of rapamycin (mTOR), a downstream target of Akt, sensitizes cancer cells to chemotherapeutic agents. As the mechanism of this sensitization, especially its relationship with p53 expression remains largely unclear; we design the present study to investigate if RAD001, a mTOR inhibitor, could enhance the chemo-cytotoxicity for HCC in cell lines with different characteristics of p53. Methods: HCC cell lines with wild type (wt) p53 (HEPG2) and mutant/null p53 (PLC/HEP3B) expression were treated with RAD001 (mTOR inhibitor) alone, cisplatin alone or combination of RAD001 and cisplatin. Cell proliferation and viability were determined by MTT assay. Apoptosis was determined by Annexin V/propidium iodide staining and analyzed by flow cytometry. Results: RAD001 suppressed tumor cell proliferation in both wt and mutant/null p53 HCC cell lines. The effect of mTOR inhibition was confirmed by the dephosphorylation of 4E-BP1 and S6K1. RAD001 enhanced cisplatin induced apoptosis in both HCC cell lines with wt and mutant/null p53 expression. mTOR inhibition in combined with cisplatin up-regulated pro-apoptotic molecules and down-regulated survival molecules. Conclusion: We have shown that inhibition of mTOR enhances cisplatin induced chemo-cytotoxicity for HCC in a p53 independent manner. These results suggest that the use of mTOR inhibitors in combination with conventional chemo-therapeutic agents may offer broad clinical benefits to HCC patients.
Persistent Identifierhttp://hdl.handle.net/10722/107753
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorTam, KHen_HK
dc.contributor.authorYang, Zen_HK
dc.contributor.authorPoon, RTPen_HK
dc.date.accessioned2010-09-26T00:10:58Z-
dc.date.available2010-09-26T00:10:58Z-
dc.date.issued2006en_HK
dc.identifier.citationThe 97th Annual Meeting of the American Association for Cancer Research, Washington D.C. 1 - 5 April 2006. In Cancer Research, 2006, v. 66 n. 8 S, Abstract no. 1352-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/107753-
dc.description.abstractObjective: Chemo-resistance is a major concern in the treatment of hepatocellular carcinoma (HCC). Several studies have demonstrated that inhibition of mammalian target of rapamycin (mTOR), a downstream target of Akt, sensitizes cancer cells to chemotherapeutic agents. As the mechanism of this sensitization, especially its relationship with p53 expression remains largely unclear; we design the present study to investigate if RAD001, a mTOR inhibitor, could enhance the chemo-cytotoxicity for HCC in cell lines with different characteristics of p53. Methods: HCC cell lines with wild type (wt) p53 (HEPG2) and mutant/null p53 (PLC/HEP3B) expression were treated with RAD001 (mTOR inhibitor) alone, cisplatin alone or combination of RAD001 and cisplatin. Cell proliferation and viability were determined by MTT assay. Apoptosis was determined by Annexin V/propidium iodide staining and analyzed by flow cytometry. Results: RAD001 suppressed tumor cell proliferation in both wt and mutant/null p53 HCC cell lines. The effect of mTOR inhibition was confirmed by the dephosphorylation of 4E-BP1 and S6K1. RAD001 enhanced cisplatin induced apoptosis in both HCC cell lines with wt and mutant/null p53 expression. mTOR inhibition in combined with cisplatin up-regulated pro-apoptotic molecules and down-regulated survival molecules. Conclusion: We have shown that inhibition of mTOR enhances cisplatin induced chemo-cytotoxicity for HCC in a p53 independent manner. These results suggest that the use of mTOR inhibitors in combination with conventional chemo-therapeutic agents may offer broad clinical benefits to HCC patients.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research-
dc.relation.ispartofCancer Researchen_HK
dc.titlemTOR inhibitor sensitizes chemo-cytotoxicity for hepatocellular carcinomaen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailYang, Z: zfyang@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.hkuros118596en_HK

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