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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
1989-6-14
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pubmed:abstractText |
The biochemical changes responsible for acquired resistance to cisplatin (DDP) are not fully understood. We have developed DDP-resistant sublines of COLO 316 human ovarian carcinoma cells in vitro and characterized a number of biochemical features of these cells. Following selection with either continuous 50 nM DDP (COLO/DDP50 cells) or intermittent 1 microM DDP (COLO/B, COLO/C, or COLO/D cells) the onset of resistance was rapid. The resistance of the COLO/B cells gradually fell from 14-fold to 5-fold over 6 months in drug-free media. Both selection procedures produced cells exhibiting broad cross-resistance to other platinum analogs, natural products and alkylating agents. There was no significant change in the growth rate (doubling time = 36 h, cloning efficiency (28%), protein content (0.55 mg/10(6) cells), or morphology of these cells. Cell cycle distributions of log-phase cells were similar (60% G0/G1, 35% S, 5% G2/M) as determined by flow cytometry. Glutathione (GSH) levels, while not elevated in COLO-B cells at low levels of resistance (2-3-fold), were 30% elevated at higher levels of resistance (9-fold). However, GSH levels in COLO/DDP50 cells with 13-fold resistance were 2.3-fold elevated. The resistance of both cell types could be partially reversed by extended depletion of GSH with D,L-buthionine-S,R-sulfoximine. COLO/D cells had a 48% decrease in DDP accumulation at 1 h while COLO/DDP50 cells had no change in DDP accumulation. The cross-resistance profiles, GSH biochemistry and DDP accumulation data indicate that acquired DDP-resistance is a complex, multifactorial response in these cells. The specific combination of mechanisms expressed in these cells appears to depend upon the selection procedure.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0277-5379
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
619-25
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2714338-Cell Line,
pubmed-meshheading:2714338-Cisplatin,
pubmed-meshheading:2714338-Drug Resistance,
pubmed-meshheading:2714338-Female,
pubmed-meshheading:2714338-Glutathione,
pubmed-meshheading:2714338-Humans,
pubmed-meshheading:2714338-Ovarian Neoplasms,
pubmed-meshheading:2714338-Tumor Cells, Cultured
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pubmed:year |
1989
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pubmed:articleTitle |
Characterization of cisplatin-resistant COLO 316 human ovarian carcinoma cells.
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pubmed:affiliation |
Cancer Center, University of California, San Diego, La Jolla 92093.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|