Antitumor Activity of Keyhole Limpet Hemocyanin on N-butyl-N-(4-hydroxybutyl) Nitrosamine Induced Bladder Carcinoma in Mice

Seon, In Chul; Kim, Sae Woong; Kang, Sung Hak

Abstract

Purpose
The antitumor activity and toxicity of keyhole limpet hemocyanin (KLH) on bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) were investigated.
Materials and Methods
Sixty 6 to 8-week-old female C3H2 mice were divided into three groups. Bladder carcinomas were induced by the addition of 0.05% BBN to the drinking water for 8 weeks. Group A received an intravesical instillation of 0.25ml KLH-free buffer, Group B received 0.5mg KLH in 0.1ml buffer subcutaneously and Group C received an intravesical instillation of 2mug KLH in 0.25ml buffer twice weekly for 8 weeks (day 15 to day 70). On day 91, all the animals were sacrificed. The tumor incidence, bladder weight and toxicity were evaluated.
Results
The incidences of cancer in groups A, B and C were 80, 40 and 60%, respectively. The incidence of cancer was significantly reduced in group B compared to group A (p<0.05). The average bladder weights were 93.63+/-17.746, 71.5+/-7.540 and 77.5+/-9.530mg in groups A, B and C, respectively. The bladder weights in groups B and C were significantly reduced compared to group A (p<0.05). There was no liver, kidney or bone marrow toxicities in groups B and C.
Conclusions
These results suggest that KLH act as an effective and safe immunotherapeutic agent for bladder cancer. Prospective randomized clinical trials should be used to evaluate the role of KLH as an immunotherapeutic agent in the prophylaxis of recurrent bladder cancer.