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Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer

2014; Nature Portfolio; Volume: 4; Issue: 1 Linguagem: Inglês

10.1038/srep04669

2045-2322

Bo Gao, Amanda J. Russell, Jonathan Beesley, Xiaohong Chen, Sue Healey, Michelle J. Henderson, Mark Wong, Catherine Emmanuel, Laura Galletta, Sharon E. Johnatty, David D.L. Bowtell, David D.L. Bowtell, Georgia Chenevix‐Trench, Anna deFazio, Dorota M. Gertig, A Green, Penelope M. Webb, Jillian A. Hung, Sue Moore, Nadia Traficante, Sián Fereday, Karen Harrap, T. Sadkowsky, Nirmala Pandeya, Robin Stuart‐Harris, Fred Kirsten, Josie Rutovitz, Peter Clingan, Amanda Glasgow, Anthony Proietto, Stephen Braye, Greg Otton, Jennifer Shannon, Tony Bonaventura, James Stewart, Stephen Begbie, Michael Friedlander, David R. Bell, Sally Baron‐Hay, Alan Ferrier, Greg Gard, David Nevell, Nick Pavlakis, Sue Valmadre, Bridget Young, C. Camaris, Roger Crouch, L. Edwards, Neville F. Hacker, Donald E. Marsden, Greg Robertson, Philip Beale, Jane Beith, Jonothan Carter, C. Dalrymple, Anne Hamilton, R. Houghton, Peter Russell, Matthew Links, John J. Grygiel, Jane Hill, Alison H. Brand, Karen Byth, Richard Jaworski, Paul R. Harnett, Raghwa Sharma, Anita Achen, Gerard Wain, Bruce G. Ward, David Papadimos, Alex J. Crandon, Margaret C. Cummings, K. Horwood, Andreas Obermair, Lewis Perrin, David Wyld, James Nicklin, Margaret Davy, Martin K. Oehler, Christopher L. Hall, Tom Dodd, Tabitha Healy, Ken Pittman, Doug Henderson, John Miller, J. Pierdes, Penny Blomfield, David Challis, Robert McIntosh, Andrew Parker, Robert Brown, Robert Rome, David G. Allen, Peter Grant, Simon Hyde, Rohan Laurie, Melissa Robbie, David Healy, Tom Jobling, Tom Manolitsas, J. McNealage, Peter A. W. Rogers, B. Susil, E. Sumithran, Ian Simpson, Kelly‐Anne Phillips, Danny Rischin, Stephen B. Fox, Daryl Johnson, Paul Waring, Stephen Lade, Maurice B. Loughrey, N. O’Callaghan, William K. Murray, Virginia Billson, Jan Pyman, Debra Neesham, Michael Quinn, Craig Underhill, Richard H. Bell, L. F. Ng, Robert Blum, Vinod Ganju, Ian Hammond, Yee Leung, Anthony J. McCartney, Martin Buck, Izak Haviv, David M. Purdie, David C. Whiteman, Nikolajs Zeps, M. Malt, Anne Mellon, Randall Robertson, Trish Vanden Bergh, Marian Jones, Patricia MacKenzie, J. Maidens, Kath Nattress, Yoke-Eng Chiew, Annie Stenlake, Helen Sullivan, Barbara M. Alexander, P. Ashover, Sue Brown, T. Corrish, L. Green, Leah Jackman, Kaltin Ferguson, Karen Martin, A. Martyn, Barbara A. Ranieri, Jo White, V. Jayde, Leanne Bowes, Pamela Mamers, Laura Galletta, Debra Giles, Joy Hendley, Katherine Alsop, Trudy Schmidt, H. Shirley, Colleen T. Ball, Cherry Young, S. Viduka, Hoa Tran, Sanela Bilic, Lydia Glavinas, Julia Brooks, Michelle Haber, Murray D. Norris, Paul R. Harnett, Georgia Chenevix‐Trench, Rosemary L. Balleine, Anna deFazio,

Pregnancy and Medication Impact

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.