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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-6-21
pubmed:abstractText
Taxol is a novel anticancer agent with activity against a broad range of tumors. It has a unique ability to stabilize polymerized tubulin into microtubule bundles within the cell. We have established a taxol-resistant human small-cell lung cancer cell line (H69/Txl) by exposing H69 cells to stepwise increases in taxol concentration. The resistance of H69/Txl cells to taxol was 4.7-fold that of the original H69 cells: the IC50 values for H69 and H69/Txl were 113.7 +/- 56.54 nM and 538.7 +/- 214.7 nM by the tetrazolium dye assay, respectively. Removal of the drug from the medium resulted in a 38% decrease in the growth rate of H69/Txl as compared with that in the presence of 30 nM taxol, suggesting that the growth of H69/Txl was partially dependent on taxol. H69/Txl showed higher sensitivity to vinca alkaloids such as vindesine, vincristine and vinblastine than the parental H69. There was no significant difference in intracellular [3H]taxol content between H69 and H69/Txl cells. No MDR-1 mRNA was detected in H69/Txl by the reverse transcription polymerase chain reaction. There was no significant difference of total and polymerized tubulin content between H69 and H69/Txl cells. Altered mobility of one of the alpha-tubulin isoforms in H69/Txl was revealed by using isoelectric focusing and Western blotting with anti-alpha-tubulin antibody. In H69, two alpha-tubulin isoforms were observed, whereas three were evident in H69/Txl, two of them comigrating with the isoforms of H69 and the other being more acidic. We observed the increased acetylation of alpha-tubulin in H69/Txl cells as compared with that in H69 cells. The acetylation of alpha-tubulin may be responsible for the taxol resistance and/or taxol-dependent growth of H69/Txl.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0910-5050
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:geneSymbol
MDR-1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
290-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Characterization of a taxol-resistant human small-cell lung cancer cell line.
pubmed:affiliation
Pharmacology Division, National Cancer Center Research Institute, Tokyo.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't