Effects of bacillus Calmette-Guerin and interferon-alpha-2B on human bladder cancer in vitro

The cytolytic and anti-proliferative effects of bacillus Calmette-Guerin (BCG) and/or interferon-alpha-2b (IFN-alpha-2b) on 5 human bladder carcinoma cell lines, RT4, RT112, MGH, SD and J82, were determined. The cell lines showed different sensitivities to BCG and IFN-alpha-2b. BCG had direct dose-dependent cytolytic and anti-proliferative effects on MGH, J82 and SD (grade 3 cell lines), whereas RT4 and RT112 (grades 1 and 2, respectively) were less sensitive. Surprisingly, higher concentrations of BCG enhanced cell growth of RT4. IFN-alpha-2b also had cytolytic and anti-proliferative effects on all 5 cell lines. Thus, the RT4 and RT112 cell lines that were not sensitive to BCG were highly sensitive to IFN-alpha-2b. A combination of BCG and IFN-alpha-2b had additive anti-proliferative effects on MGH, J82 and RT112. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production by these 5 cell lines was measured after stimulation with BCG and/or IFN-alpha-2b, by ELISA immunoassays. Production of IL-6 and TNF-alpha was significantly increased in MGH and J82 cell lines by the combination of BCG and IFN alpha-2b. The enhanced cytolytic and anti-proliferative effects of the combination of BCG and IFN-alpha-2b may be related to the induction of cytokines.