The effects of meglumine gamma linolenic acid (MeGLA) on an organ culture model of superficial bladder cancer.
The objective of this research was to assess the effects of the novel intravesical drug MeGLA in a physiologically representative model of superficial bladder cancer. Petri dishes were used to culture 5 mm square explants of rat bladder in minimal volumes of supplemented culture medium. Parental and resistant MGH-U1 urothelial cancer cells were transfected with a green fluorescent protein (GFP) vector. Transfectants were purified by flow cytometry. Cells were seeded onto the prepared organ cultures and imaging was performed using confocal microscopy. Confirmation of the tumour colonies was done using scanning electron microscopy. MeGLA was added at various concentrations to the colonies and its effects noted over several days. Results showed that colonies of GFP-MGH-U1 cells established themselves on the explants and could be identified by confocal microscopy. The colonies could then be followed over several days. The colonies were able to survive high concentrations of the drug of up to 1 mg/ml, 400 times the IC > 90% for monolayers and equivalent to doses in clinical use. We conclude that MeGLA is less effective in this system than on monolayer cell lines. However, it showed cytotoxic effects which were comparable to those seen with conventional agents in the same system.
Crook
T J
TJ
Dept of Urology, Southampton General Hospital, UK. timjcrook@chandlers69.freeserve.co.uk
Dyer
J P
JP
McCormick
R I
RI
Birch
B R
BR
Cooper
A J
AJ
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008536:Meglumine / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017965:gamma-Linolenic Acid / Q000627:therapeutic use*
D008536:Meglumine; D017965:gamma-Linolenic Acid