Article: Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma
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- Publisher Website: 10.1016/j.canlet.2008.08.018
- Scopus: eid_2-s2.0-57349106607
- PMID: 18824293
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| Title | Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Tam, KH1 Yang, ZF1 Lau, CK1 Lam, CT1 Pang, RWC1 Poon, RTP1 | ||||||
| Keywords | Chemoresistance Chemosensitivity HCC mTOR p53 RAD001 | ||||||
| Issue Date | 2009 | ||||||
| Publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet | ||||||
| Citation | Cancer Letters, 2009, v. 273 n. 2, p. 201-209 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.canlet.2008.08.018 | ||||||
| Abstract | The present study investigated the effect of mammalian target of rapamycin (mTOR) inhibition on HCC cells in vitro and in vivo, either alone or in combination with cytotoxic agents. In vitro, HCC cell lines were exposed to RAD001, an mTOR inhibitor, either alone or in combination with cisplatin. Alone, RAD001 suppressed cell proliferation in all cell lines tested, but did not induce apoptosis. RAD001 in combination with cisplatin induced a significant increase in the number of apoptotic cells, downregulated the expression of pro-survival molecules, Bcl-2, survivin and cyclinD1, and increased the cleavage of PARP, compared to RAD001 or cisplatin alone. Transfection of p53 into the Hep3B cell line increased the sensitivity of tumor cells to cisplatin. The suppression of HCC tumor growth in vivo was enhanced by RAD001 combined with cisplatin, accompanied by a significant increase in the number of apoptotic cells in tumor tissues. This study demonstrates that inhibition of mTOR suppresses tumor growth and sensitizes tumor cells to chemocytotoxic agents. © 2008 Elsevier Ireland Ltd. All rights reserved. | ||||||
| ISSN | 0304-3835 2011 Impact Factor: 4.238 2011 SCImago Journal Rankings: 0.494 | ||||||
| DOI | http://dx.doi.org/10.1016/j.canlet.2008.08.018 | ||||||
| ISI Accession Number ID | WOS:000262582100003
Funding Information: The study was supported by the Seed Funding Program for Basic Research 2006 and Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery of the University of Hong Kong. | ||||||
| References | References in Scopus |
| dc.contributor.author | Tam, KH | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Yang, ZF | ||||||
| dc.contributor.author | Lau, CK | ||||||
| dc.contributor.author | Lam, CT | ||||||
| dc.contributor.author | Pang, RWC | ||||||
| dc.contributor.author | Poon, RTP | ||||||
| dc.date.accessioned | 2010-05-31T03:44:03Z | ||||||
| dc.date.available | 2010-05-31T03:44:03Z | ||||||
| dc.date.issued | 2009 | ||||||
| dc.description.abstract | The present study investigated the effect of mammalian target of rapamycin (mTOR) inhibition on HCC cells in vitro and in vivo, either alone or in combination with cytotoxic agents. In vitro, HCC cell lines were exposed to RAD001, an mTOR inhibitor, either alone or in combination with cisplatin. Alone, RAD001 suppressed cell proliferation in all cell lines tested, but did not induce apoptosis. RAD001 in combination with cisplatin induced a significant increase in the number of apoptotic cells, downregulated the expression of pro-survival molecules, Bcl-2, survivin and cyclinD1, and increased the cleavage of PARP, compared to RAD001 or cisplatin alone. Transfection of p53 into the Hep3B cell line increased the sensitivity of tumor cells to cisplatin. The suppression of HCC tumor growth in vivo was enhanced by RAD001 combined with cisplatin, accompanied by a significant increase in the number of apoptotic cells in tumor tissues. This study demonstrates that inhibition of mTOR suppresses tumor growth and sensitizes tumor cells to chemocytotoxic agents. © 2008 Elsevier Ireland Ltd. All rights reserved. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Cancer Letters, 2009, v. 273 n. 2, p. 201-209 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.canlet.2008.08.018 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.canlet.2008.08.018 | ||||||
| dc.identifier.epage | 209 | ||||||
| dc.identifier.hkuros | 154431 | ||||||
| dc.identifier.isi | WOS:000262582100003
Funding Information: The study was supported by the Seed Funding Program for Basic Research 2006 and Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery of the University of Hong Kong. | ||||||
| dc.identifier.issn | 0304-3835 2011 Impact Factor: 4.238 2011 SCImago Journal Rankings: 0.494 | ||||||
| dc.identifier.issue | 2 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 18824293 | ||||||
| dc.identifier.scopus | eid_2-s2.0-57349106607 | ||||||
| dc.identifier.spage | 201 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/59161 | ||||||
| dc.identifier.volume | 273 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet | ||||||
| dc.publisher.place | Ireland | ||||||
| dc.relation.ispartof | Cancer Letters | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Cancer Letters. Copyright © Elsevier Ireland Ltd. | ||||||
| dc.subject | Chemoresistance | ||||||
| dc.subject | Chemosensitivity | ||||||
| dc.subject | HCC | ||||||
| dc.subject | mTOR | ||||||
| dc.subject | p53 | ||||||
| dc.subject | RAD001 | ||||||
| dc.title | Inhibition of mTOR enhances chemosensitivity in hepatocellular carcinoma | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong