Establishment and characterization of a bladder cancer cell line with enhanced doxorubicin resistance by mevalonate pathway activation
2015
Abstrakt
A doxorubicin-resistant variant of the bladder cancer cell line BFTC-905 has been established and characterized. These cells (BFTC-905-DOXO-II) exhibit enhanced clonogenicity and diminished apoptosis, but no enhanced efflux of the drug.
Array-based gene expression analysis disclosed a permanent activation of the mevalonate biosynthetic pathway in the chemoresistant daughter cells. Pharmacological blocking of the mevalonate pathway with simvastatin lead to complete reversal of the chemoresistance.
As statins are well characterized and widely used drugs, this new application of statins could be clinically relevant in the subset of chemoresistant tumours.