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Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression.
Sublines from the small cell lung cancer (SCLC) cell lines U1285 and U1690, denoted U1285-100, U1285-250, U1690-40 and U1690-150, were adapted to grow in the continuous presence of 100, 250, 40 and 150 ng ml-1 doxorubicin (Dox), respectively. The Dox resistance was accompanied by cross-resistance to...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
1991
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977853/ https://www.ncbi.nlm.nih.gov/pubmed/1684906 |
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author | Nygren, P. Larsson, R. Gruber, A. Peterson, C. Bergh, J. |
author_facet | Nygren, P. Larsson, R. Gruber, A. Peterson, C. Bergh, J. |
author_sort | Nygren, P. |
collection | PubMed |
description | Sublines from the small cell lung cancer (SCLC) cell lines U1285 and U1690, denoted U1285-100, U1285-250, U1690-40 and U1690-150, were adapted to grow in the continuous presence of 100, 250, 40 and 150 ng ml-1 doxorubicin (Dox), respectively. The Dox resistance was accompanied by cross-resistance to vincristine (Vcr), Vp-16 and for U1285-100 also to cisplatinum. Sublines of U1690-40 and U1285-100, cultured in absence of Dox for 4 months were only partially reversed with respect to Dox resistance. Neither the parental nor the most Dox resistance sublines had detectable levels of mdr 1 RNA but a small fraction of cells in all cell lines stained weakly positive for P-glycoprotein (P-gp). Verapamil (Ver) at 5 microM reversed the Dox resistance completely and partly in the U1690 and U1285 sublines, respectively, but did not increase the cellular accumulation of Dox. The cytoplasmic free Ca2+ concentration (Ca2+i) was close to 100 nM in both parental cell lines but elevated in the U1285-100 and U1690-40 sublines by 21 and 44%, respectively, and in U1285-250 and U1690-150 by 51 and 91%, respectively. The partly reverted sublines still showed significant but smaller elevations in Ca2+i of 10-30%. Ver was without acute or long term effects of Ca2+i in the U1285-100 and U1690-40 sublines. Selection for Dox resistance in SCLC may thus result in atypical multidrug-resistance characterised by absence of P-gp overexpression and atypical cross-resistance. Although Ver did not seem to affect Dox accumulation it may still work as a resistance modulator.(ABSTRACT TRUNCATED AT 250 WORDS) |
format | Text |
id | pubmed-1977853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1991 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-19778532009-09-10 Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression. Nygren, P. Larsson, R. Gruber, A. Peterson, C. Bergh, J. Br J Cancer Research Article Sublines from the small cell lung cancer (SCLC) cell lines U1285 and U1690, denoted U1285-100, U1285-250, U1690-40 and U1690-150, were adapted to grow in the continuous presence of 100, 250, 40 and 150 ng ml-1 doxorubicin (Dox), respectively. The Dox resistance was accompanied by cross-resistance to vincristine (Vcr), Vp-16 and for U1285-100 also to cisplatinum. Sublines of U1690-40 and U1285-100, cultured in absence of Dox for 4 months were only partially reversed with respect to Dox resistance. Neither the parental nor the most Dox resistance sublines had detectable levels of mdr 1 RNA but a small fraction of cells in all cell lines stained weakly positive for P-glycoprotein (P-gp). Verapamil (Ver) at 5 microM reversed the Dox resistance completely and partly in the U1690 and U1285 sublines, respectively, but did not increase the cellular accumulation of Dox. The cytoplasmic free Ca2+ concentration (Ca2+i) was close to 100 nM in both parental cell lines but elevated in the U1285-100 and U1690-40 sublines by 21 and 44%, respectively, and in U1285-250 and U1690-150 by 51 and 91%, respectively. The partly reverted sublines still showed significant but smaller elevations in Ca2+i of 10-30%. Ver was without acute or long term effects of Ca2+i in the U1285-100 and U1690-40 sublines. Selection for Dox resistance in SCLC may thus result in atypical multidrug-resistance characterised by absence of P-gp overexpression and atypical cross-resistance. Although Ver did not seem to affect Dox accumulation it may still work as a resistance modulator.(ABSTRACT TRUNCATED AT 250 WORDS) Nature Publishing Group 1991-12 /pmc/articles/PMC1977853/ /pubmed/1684906 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Nygren, P. Larsson, R. Gruber, A. Peterson, C. Bergh, J. Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression. |
title | Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression. |
title_full | Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression. |
title_fullStr | Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression. |
title_full_unstemmed | Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression. |
title_short | Doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic Ca2+ and resistance modulation by verapamil in absence of P-glycoprotein overexpression. |
title_sort | doxorubicin selected multidrug-resistant small cell lung cancer cell lines characterised by elevated cytoplasmic ca2+ and resistance modulation by verapamil in absence of p-glycoprotein overexpression. |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1977853/ https://www.ncbi.nlm.nih.gov/pubmed/1684906 |
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