Pseudomonas aeruginosa Vaccine Induces Apoptosis in Human Hepatoma Cells Through Mitochondrial and Death Receptor Pathways

Background: Pseudomonas aeruginosa (PA) is a common cause of chronic infection in patients including tumor patients. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) is a vaccine based on PA. However, the effect of PA-MSHA on tumorigenesis is rarely studied. In this paper, we investigated the effects and mechanisms of action for PA-MSHA in human hepatoma cells. Methods: The cell growth inhibition rate of human hepatoma HepG-2 cells after treatment with PA-MSHA was determined by MTT assay. The apoptosis of carcinoma cells was detected by Fluorescent labeling method and TUNEL method. The cell ultrastructure was investigated under the electron microscope. The protein expressions of Bcl-2, bax, Fas, FasL, Caspase-3, Caspase-8 and Caspase-9 were detected by Western blotting. Furthermore, the anti-tumor activity of PA-MSHA was assessed by xenograft in nude mice. Results: PA-MSHA inhibited the growth of HepG-2 cells in a time- and dose-dependent manner. HepG-2 cells treated with PA-MSHA were obviously out of shape, presenting some typical morphologic features of apoptosis, which were confirmed by electron microscope. The apoptotic rates were significantly increased in the experimental groups compared to the control group. PA-MSHA up regulated the expression of Bax, Fas, Caspase-3, Caspase-8 and Caspase-9 and down-regulated the expression of Bcl-2 and FasL in HepG2 cells. Importantly, PA-MSHA greatly inhibited the tumor growth in vivo. Conclusion: PA-MSHA suppressed the hepatoma cell growth by induction of tumor cell apoptosis through mitochondria! and death receptor pathways.