Tumor inhibitory effects of intravesical Ganoderma lucidum instillation in the syngeneic orthotopic MB49/C57 bladder cancer mice model

Abstract

Ethnopharmacological relevance: Ganoderma lucidum (GL) has been traditionally used in oriental medicine as superior health tonic, and there are numerous scientific evidences of its antitumorigenic activities. Aim of the study: To evaluate the intravesical chemopreventive effects of ethanol extract of GL (GLe) on bladder cancer. . Materials and methods: Intravesical therapy is defined as the direct instillation of a liquid drug into bladder through a catheter. Bacille Calmette-Guerin (BCG) solution is applied intravesically as a conventional immunotherapy for preventing recurrence of bladder cancer. By adopting the MB49/C57 bladder cancer mice model, an overall 60 MB49-implanted mice were randomized into 3 groups and treated according to 3 treatment arms, including GLe, BCG and PBS. Additionally, wild-type mice without MB49 cell inoculation and treated with PBS were used as the negative control group. Testing agents were instilled intravesically for 2 h and repeated after one week for evaluating the effects on preventing the tumor formation and growth. The treated-mice were closely monitored for major adverse effects. Results: GLe demonstrated more potent cytotoxic effects than BCG on MB49 cells, although both in dose-dependent manner. In the MB49-implanted mice, 80 pg/ml GLe was shown to delay the tumor formation by one week, whereas the averaged tumor volume measured at endpoint was 3.6-fold and 4.6-fold smaller than that of the BCG or PBS, respectively. However, no significant effects were observed on body weight and hematuria. Conclusion: Current findings in mice suggested intravesical GLe therapy as an effective and safe chemopreventive strategy for inhibiting bladder tumor formation.