Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation

Greife, Annemarie and Tukova, Jitka and Steinhoff, Christine and Scott, Simon D. and Schulz, Wolfgang A. and Hatina, Jiri (2015) Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation. Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation, 36 (5). pp. 3293-3300. ISSN 1010-4283. E-ISSN 1423-0380. (doi:https://doi.org/10.1007/s13277-014-2959-9) (Full text available)

PDF (Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation) - Author's Accepted Manuscript
Download (406kB) Preview
[img]
Preview
Official URL
https://doi.org/10.1007/s13277-014-2959-9

Abstract

Resistance to chemotherapy is a major problem in the treatment of urothelial bladder cancer. Several mechanisms have been identified in resistance to doxorubicin by analysis of resistant urothelial carcinoma (UC) cell lines, prominently activation of drug efflux pumps and diminished apoptosis. We have derived a new doxorubicin-resistant cell line from BFTC-905 UC cells, designated BFTC-905DOXO-II. A doxorubicin-responsive green fluorescent protein (GFP) reporter assay indicated that resistance in BFTC905-DOXO-II was not due to increased drug efflux pump activity, whereas caspase-3/7 activation was indeed diminished. Gene expression microarray analysis revealed changes in proapoptotic and antiapoptotic genes, but additionally induction of the mevalonate (cholesterol) biosynthetic pathway. Treatmentwithsimvastatin restored sensitivity of BFTC-905DOXO-II to doxorubicin to that of the parental cell line. Induction of the mevalonate pathway has been reported as a mechanism of chemoresistance in other cancers; this is the first observation in bladder cancer. Combinations of statins with doxorubicin-containing chemotherapy regimens may provide a therapeutic advantage in such cases

Item Type: Article
Uncontrolled keywords: Bladder cancer, Chemotherapy, Doxorubicin resistance, Mevalonatepathway
Subjects: Q Science
R Medicine
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Simon Scott
Date Deposited: 30 Nov 2017 12:42 UTC
Last Modified: 04 Dec 2017 10:54 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/46759 (The current URI for this page, for reference purposes)
Scott, Simon D.: https://orcid.org/0000-0002-8290-0461
  • Depositors only (login required):

Downloads

Downloads per month over past year