Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer
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(Published version)
Date
2014
Authors
Gao, B.
Russell, A.
Beesley, J.
Chen, X.
Healey, S.
Henderson, M.
Wong, M.
Emmanuel, C.
Galletta, L.
Johnatty, S.
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Journal article
Citation
Scientific Reports, 2014; 4(1):4669-1-4669-9
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Bo Gao, Amanda Russell, Jonathan Beesley, Xiao Qing Chen, Sue Healey, Michelle Henderson, Mark Wong, Catherine Emmanuel, Laura Galletta, Sharon E. Johnatty, David Bowtell, Australian Ovarian Cancer Study Group, Michelle Haber, Murray Norris, Paul Harnett, Georgia Chenevix-Trench, Rosemary L. Balleine, Anna deFazio
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Abstract
ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may underlie the association. Using cell-based models, we evaluated the correlations between ABCB1 expression, polymorphisms, transporter activity and paclitaxel sensitivity in ovarian cancer (n = 10) and lymphoblastoid (n = 19) cell lines. Close associations between ABCB1 expression, transporter function and paclitaxel sensitivity were found in lymphoblastoid cell lines, although we could not demonstrate an association with common SNPs. In ovarian cancer cell lines, ABCB1 expression was low and the association between expression and function was lost. These results suggest that ABCB1 related survival difference in ovarian cancer patients is more likely to be due to differential whole body paclitaxel clearance mediated by normal cells rather than a direct effect on cancer cells.
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Martin Oehler is a member of the Australian Ovarian Cancer Study Group
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