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Progesterone: a novel adjunct to intravesical chemotherapy
Author(s) -
Lewin J.,
Cooper A.,
Birch B.
Publication year - 2002
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.2002.03013.x
Subject(s) - epirubicin , cell culture , cisplatin , cytotoxic t cell , multiple drug resistance , cytotoxicity , urothelial cell , cancer research , chemistry , chemotherapy , pharmacology , medicine , in vitro , biology , urinary bladder , drug resistance , urothelium , cyclophosphamide , biochemistry , microbiology and biotechnology , genetics
Objective To investigate the effect of progesterone on multidrug‐resistant urothelial cell lines, as the failure of intravesical chemotherapeutic drugs is often caused by multidrug resistance (MDR), mediated by the drug efflux pump P‐glycoprotein (PGP), the function of which can be down‐regulated by various compounds including steroid hormones. Materials and methods Two urothelial cell lines (RT112S and MGH‐U 1 S) and their MDR sublines (RT112R, to cisplatin; and MGH‐U 1 R, a cell line expressing PGP) were used to assess the cytotoxic effects of progesterone, epirubicin and their combination. Cytotoxicity was assessed using a tetrazolium‐based assay and in situ confocal microscopy. Results Cell lines sensitive to epirubicin (MGH‐U 1 S, RT112S and RT112R) required a much lower dose of epirubicin to kill half the cells than did the MDR cell line. Progesterone was intrinsically cytotoxic to all cell lines with little difference among them. Combined therapy had no cumulative effect on epirubicin‐sensitive cell lines, but reversed MDR in the MGHU 1 R cell line, both assessed by confocal microscopy and by the tetrazolium assay. Conclusions Progesterone can reverse MDR in urothelial cells in vitro . This, combined with its effects on cell differentiation and apoptosis, together with its safety and tolerability compared to other MDR agents, suggests it may be a valuable adjunct to intravesical chemotherapy.