Peripheral blood mononuclear cells inhibit proliferation and promote apoptosis of HeLa cells following stimulation with Bacillus Calmette-Guerin

Bacillus Calmette-Guerin (BCG) immunotherapy is established as an effective adjuvant intravesical treatment for non-muscle invasive bladder cancer. BCG is also effective in the treatment of Condylomata acuminata caused by low-risk human papilloma virus (HPV). The aim of this study was to determine the efficacy of BCG for the treatment of cervical cancer or HPV high-risk infections. BCG-activated killer (BAK) cells were incubated with a high-risk HPV18-infected cervical cancer cell line, HeLa. The cell cycle distribution and apoptotic index of the HeLa cells were analyzed by flow cytometry. The alterations of HPV-E7, retinoblastoma (RB) and E2F1 levels were detected at the transcriptional and translational levels. The BAK cell cytotoxicity to HeLa cells was 24.08, 14.74 and 6.8% and the natural killer (NK) cell cytotoxicity was 17.62, 10.78 and 5.8% at the E/T ratios of 40:1, 20:1 and 10:1, respectively. The BAK cells significantly induced the apoptosis of HeLa cells to result in an apoptosis level of 24.2% compared with 13.45% by the NK cell treatment at the ratio of 20:1. BAK cells inhibit the proliferation of HeLa cells by G(1)/S cell cycle arrest and this may be associated with the RB/E2F1 pathway. However, G(1)/S arrest and the alteration of RB protein (pRB) and E2F1 levels in the HeLa cells did not show significant differences between the BAK cell- and NK cell-treated groups. HPV-E7 appeared not to be associated with the alteration in cell cycle progression. This study showed that immunotherapy may be a potential treatment for cervical cancer and that BCG immunotherapy may be an alternative and effective method, but further experiments and clinical trials are required to verify this effect.