Published online Nov 30, 2006.
https://doi.org/10.4111/kju.2006.47.11.1155
Anticancer Activity of Intravesical Glyceryl Monooleate (GMO)-Paclitaxel Therapy in Murine Superficial Transitional Cell Carcinoma Model Induced by BBN
Abstract
Purpose
Paclitaxel, on systemic administration, is widely known to be effective in the treatment of bladder cancer. However, the intravesical use of paclitaxel has not been attempted because of its liposolubility and direct toxicity to the bladder mucosa. The purpose of this study was to evaluate the efficacy and toxicity of paclitaxel-loaded glyceryl monooleate (GMO) in the intravesical treatment of superficial bladder cancer, by enhancing its bioadhesiveness and bioavailability.
Materials and Methods
12 mice were divided into two groups, and bladder carcinomas induced by the addition of 0.05% BBN to their drinking water for 12 weeks. Group 1 received an intravesical instillation of 0.1ml GMO-paclitaxel-free buffer and Group 2 an intravesical instillation of 0.1ml GMO-paclitaxel. On day 21, the tumor incidence, bladder weight and toxicity were evaluated.
Results
The incidence of cancer in groups 1 and 2 were 83 and 17%, respectively. The incidence of cancer was significantly reduced in group 2 compared to group 1 (p<0.05). There was a tendency for the average bladder weight in group 1 to be heavier than that in group 2, but there was no significant difference (p=0.375). There were no liver, kidney or bone marrow toxicities in either group.
Conclusions
Intravesical GMO-paclitaxel therapy may have an inhibitory effect on the growth of superficial bladder cancer in a BBN-induced bladder cancer model; therefore, it could potentially be used in those patients showing little to no response to intravesical Bacillus Calmette-Guerin (BCG) or other anticancer drug therapies.
Fig. 1
Histological aspects of bladders from mice on day 21 after intravesical instillation therapy (A). The tumor growth in group I shows disrupted epithelium (H&E, ×100). (B) No tumor growth is found in group II (H&E, ×100).
Fig. 2
Effect of intravesical glyceryl monooleate (GMO)-paclitaxel on the urinary bladder weight. The bladder weight distribution is presented. The black line inside the box identifies the group median. The glyceryl monooleate (GMO)-paclitaxel treatment group shows a lower mean value, but there are no significant differences between the two groups (p=0.375, Mann-Whitney-U-test). PBS: phosphate buffered saline.
Fig. 3
Histological findings of the liver (A) and kidney (B) from a mouse after intravesical instillation of glyceryl monooleate (GMO)-paclitaxel show neither abnormality nor toxicity (H&E, ×100).
Fig. 4
Peripheral blood (A) and bone marrow (B) from a mouse after intravesical instillation of glyceryl monooleate (GMO)-paclitaxel show neither abnormality nor toxicity (H&E, ×100).
Table 1
Effects of intravesical chemotherapy with glyceryl monooleate (GMO)-paclitaxel on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder cancer
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