Paclitaxel sensitization of multidrug-resistant cells to chemotherapy is independent of the cell cycle.

Locke, V; Davey, R; Davey, M

Paclitaxel sensitization of multidrug-resistant cells to chemotherapy is independent of the cell cycle.

Locke, V Davey, R Davey, M

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Publication Type:: Journal Article
Citation:: Cytometry, 2001, 43 (3), pp. 170 - 174
Issue Date:: 2001-03-01

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Field	Value	Language
dc.contributor.author	Locke, V	en_US
dc.contributor.author	Davey, R	en_US
dc.contributor.author	Davey, M	en_US
dc.date.issued	2001-03-01	en_US
dc.identifier.citation	Cytometry, 2001, 43 (3), pp. 170 - 174	en_US
dc.identifier.issn	0196-4763	en_US
dc.identifier.uri	http://hdl.handle.net/10453/3697
dc.description.abstract	BACKGROUND: Recent studies have shown that paclitaxel (Taxol) is an active chemotherapeutic in the treatment of small cell lung cancer. Paclitaxel binds to tubulin and prevents depolymerization. This causes cells to arrest in the G(2)/M phase of the cell cycle, resulting in sensitization of cells to drug or radiation treatment. METHODS: A drug-resistant H69 small cell lung cancer subline was established. Cytotoxicity of cisplatin and chlorambucil was determined using the MTT cell viability assay and distribution of DNA in the cell cycle. DNA distribution was analyzed by flow cytometry after treatment with paclitaxel or the other tubulin-binding drugs, vinblastine and navelbine. RESULTS: The H69-EPR drug-resistant subline was resistant to epirubicin (sixfold) and was cross-resistant to cisplatin (7.5-fold) and chlorambucil (7.5-fold). Pretreatment with paclitaxel or vinblastine, but not navelbine, sensitized the subline to cisplatin and chlorambucil (P < 0.05), with no effect on parental H69 cells. Sensitization was dose dependent and occurred at doses below those that caused a G(2)/M block in the cell cycle. CONCLUSION: Sensitization of drug-resistant cells by paclitaxel was not associated with its ability to cause a G(2)/M block in the cell cycle. Sensitization by paclitaxel and vinblastine, but not navelbine, which preferentially targets mitotic tubulin, suggests that sensitization may involve changes in the tubulin-dependent intracellular transport processes rather than changes in mitotic tubulin and the G(2)/M block.	en_US
dc.language	eng	en_US
dc.relation.ispartof	Cytometry	en_US
dc.subject.mesh	Tumor Cells, Cultured	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Carcinoma, Small Cell	en_US
dc.subject.mesh	Lung Neoplasms	en_US
dc.subject.mesh	Cisplatin	en_US
dc.subject.mesh	Paclitaxel	en_US
dc.subject.mesh	Chlorambucil	en_US
dc.subject.mesh	Camptothecin	en_US
dc.subject.mesh	Vinblastine	en_US
dc.subject.mesh	Genistein	en_US
dc.subject.mesh	Amsacrine	en_US
dc.subject.mesh	Daunorubicin	en_US
dc.subject.mesh	Epirubicin	en_US
dc.subject.mesh	Antineoplastic Agents	en_US
dc.subject.mesh	Drug Resistance, Multiple	en_US
dc.subject.mesh	Cell Cycle	en_US
dc.subject.mesh	Cell Survival	en_US
dc.subject.mesh	Vinorelbine	en_US
dc.title	Paclitaxel sensitization of multidrug-resistant cells to chemotherapy is independent of the cell cycle.	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	43	en_US
utslib.location.activity	United States	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	43	en_US

Abstract:

BACKGROUND: Recent studies have shown that paclitaxel (Taxol) is an active chemotherapeutic in the treatment of small cell lung cancer. Paclitaxel binds to tubulin and prevents depolymerization. This causes cells to arrest in the G(2)/M phase of the cell cycle, resulting in sensitization of cells to drug or radiation treatment. METHODS: A drug-resistant H69 small cell lung cancer subline was established. Cytotoxicity of cisplatin and chlorambucil was determined using the MTT cell viability assay and distribution of DNA in the cell cycle. DNA distribution was analyzed by flow cytometry after treatment with paclitaxel or the other tubulin-binding drugs, vinblastine and navelbine. RESULTS: The H69-EPR drug-resistant subline was resistant to epirubicin (sixfold) and was cross-resistant to cisplatin (7.5-fold) and chlorambucil (7.5-fold). Pretreatment with paclitaxel or vinblastine, but not navelbine, sensitized the subline to cisplatin and chlorambucil (P < 0.05), with no effect on parental H69 cells. Sensitization was dose dependent and occurred at doses below those that caused a G(2)/M block in the cell cycle. CONCLUSION: Sensitization of drug-resistant cells by paclitaxel was not associated with its ability to cause a G(2)/M block in the cell cycle. Sensitization by paclitaxel and vinblastine, but not navelbine, which preferentially targets mitotic tubulin, suggests that sensitization may involve changes in the tubulin-dependent intracellular transport processes rather than changes in mitotic tubulin and the G(2)/M block.

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http://hdl.handle.net/10453/3697