Background: CYP26a1, 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.
Objectives: The 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.
Methods: After 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.
Results: The 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.
Conclusion: Our 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.
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