The antitumor immunopreventive effects of a DNA vaccine against CYP26a1 on mouse breast carcinoma

BackgroundCYP26a1, which functioned mainly as a retinoic acid (RA) catabolic enzyme, has been shown to be oncogenic and to support cell survival in many breast carcinoma cells.ObjectivesThe purpose of the study was to investigate the antitumor effect of a DNA vaccine targeting CYP26a1 on breast tumors development in mice which highly express CYP26a1 and to further clarify its potential mechanism.MethodsAfter three times immunization of the DNA vaccine, the BALB/c mice were inoculated with the engineered 4T1 breast cancer cells expressing CYP26a1. Primary tumors were measured every 4 days after tumor cell inoculation. The primary tumors were surgically removed and weighted after 30 days of inoculation. The anti-CYP26a1 antibody titer of the antiserum was measured by an enzyme-linked immunosorbent assay (ELISA). The effect of the vaccine on apoptosis of the primary tumor was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Apoptosis-related proteins in primary tumor were detected by Western blotting. The expression of the Th1 and Th2 type cytokines was detected by RT-PCR.ResultsThe vaccine could elicit the production of anti-CYP26a1 antibody and significantly inhibit the growth of the primary tumor compared to the control groups (p < 0.05). The vaccine induced the apoptosis of the primary tumor with the increase in expression of apoptosis-related proteins p53, Caspase3 and Fas. Furthermore, the vaccine increased the expression of the Th1 cytokine, but not the expression of Th2 cytokine.ConclusionOur study shows that the vaccine targeting CYP26a1 significantly inhibits the primary tumor growth and progression by activating the apoptosis pathway and by eliciting both humoral and cellular immune responses.

► We constructed a breast cancer mice model which highly expressed CYP26a1. ► We explored a DNA vaccine targeting CYP26a1. ► The vaccine targeting CYP26a1 significantly inhibited the tumor growth. ► The vaccine could elicit both humoral and cellular immune responses. ► The vaccine could activate the apoptosis pathway.