We have examined the cytotoxic effect of gemcitabine in intravesical therapy using an in vitro co-cultured spheroid model composed of transitional cell carcinoma (TCC) and fibroblasts from both human and rat species. Immunohistochemistry analysis of the co-cultured spheroids, using cytokeratin-13 and vimentin antibodies against TCC and fibroblasts, respectively, showed the central location of fibroblasts within the spheroid, whereas TCC formed the peripheral layers. Spheroids composed of human TCC and fibroblasts (MGH-U3/CRL-1120 or RT-112/CRL-1120) as well as rat TCC and their corresponding fibroblasts (AY-27/RF-Ed1) displayed the same drug tolerance profile after an exposure of 0, 1, 3, 5, 7 and 14 days. As confirmed by time-lapse photography, MTT essay and vital dye staining, gemcitabine selectively killed the human and rat bladder cancer cell lines, but did not affect un-transformed human and rat fibroblast lines.
1Department of Experimental Surgery and Division of Urology, University of Alberta and Department of Surgery, Cross Cancer Institute, Edmonton, Alberta 6G 1Z2, Canada
2Department of Oncology, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada
The financial support ‘in part’ was provided by the Alberta Heritage Foundation of Medical Research and the Alberta Cancer Board. Gemcitabine was gift from Eli Lilly, Inc, Indianapolis, IN.
Correspondence to RB Moore, Department of Surgery, University of Alberta, 2D2.17 Walter Mackenzie Health Sciences Center, Edmonton, Alberta T6G 2R7, Canada.
Tel: (+1) 780 492-6330; Fax: (+1) 780 492-4923;
Received 20 March 2002 accepted 16 April 2002