BCG VACCINE ACTIVATES NF-ΚB THROUGH DECTIN-1 RECEPTOR EXPRESSED ON THE EPITHELIUM OF BLADDER CANCER TO INITIATE IMMUNE RESPONSE TO PREVENT AND TREAT BLADDER CANCER

Li Wang^#, Xin Rui^#, Huafeng Pan, Zhongliang Cheng, Ling Lin, Xiaoming Xu^* 

Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), Ningbo 315000, PR China 

Objective: To study the effect of the BCG vaccine on the prevention and treatment of bladder cancer by activating NF-κB through the dendritic cell-related C-type phytohemagglutinin-1 (Dectin-1) receptor expressed in bladder cancer epithelium. 

Methods: The human bladder cancer T24 cell line was cultured in vitro, and the expression of Dectin-1 in bladder cancer cells was detected using the western blot method. BCG vaccines at dosages of 0, 0.1, 1, 2, 10 and 20g/L were used to stimulate bladder cancer cells on hours 1, 2, 4, 8 and 12, respectively. The expression of NF-κB in cells was recorded before and after blocking Dectin-1. The level of interleukin (IL-6) and tumor necrosis factor-α in the cell supernatant before and after blocking Dectin-1 (TNF-α) was analyzed using ELISA. 

Results: The expression of Dectin-1 protein in bladder cancer cells was significantly higher than in normal bladder tissues (P<0.05). Expression of NF-κB was the highest following stimulation of bladder cancer cells with 1.0g/L of BCG vaccine for one hour with the most significant activation; the expression level decreased over treatment time. The expression level of NF-κB was highest in the simple BCG stimulation group. Following blocking of Dectin-1, the expression level of NF-κB decreased, however it remained higher than that of both the simple stimulation group and the control group. Bladder cancer cells were stimulated with various dosages of BCG for two hours. ELISA test results showed that except for the 0g/L dose, IL-6 and TNF-α concentrations were significantly lower after blocking Dectin-1 (P<0.05). 

Conclusions: Dectin-1 is key to treating bladder cancer with the BCG vaccine. BCG may activate NF-κB through the Dectin-1 receptor expressed in the epithelium of bladder cancer tissue to initiate an immune response that will ultimately prevent and treat bladder cancer. The results of this study provide an experimental basis for revealing the anti-tumor mechanism of BCG.