Cytotoxic effects of recombinant adenovirus p53 and cell cycle regulator genes (p21(WAF1/CIP1) and p16(CDKN4)) in human prostate cancers

Purpose: Overexpressing or restoring the basal levels of tumor suppressor genes in cancer cells can suppress tumorigenicity of cancer cells. In this communication, we compared tumor suppressive activities of three well-defined tumor suppressive genes (p53, p21(WAF1/CIP1), and p16(CDKN2)) delivered individually to prostate cancer cells with adenoviral vector (Ad). Materials and Methods: Efficacy of growth inhibition by recombinant adenoviruses bearing p53, p21(WAF1/CIP1), or p16(CDKN2) (Ad5CMV-p53, Ad5CMV-p21, Ad5CMV-p16) genes were tested in vitro on androgen-dependent (LNCaP) and androgen-independent (C4-2, DU-145, and PC-3) human prostate cancer cells, ex vivo and in vivo on PC-3 tumor. Results: Ad5CMV-p53 was observed to exert the greatest growth inhibitory action on all of the cell lines tested; inhibition appeared to be cytolytic. In comparison to control Ad5CMV-PA added samples, the growth inhibitory action of Ad5CMV-p21 and Ad5CMV-p16 appeared to be cytostatic. Ad5CMV-p53 is more effective than Ad5CMV-p16 and Ad5CMV-p21 in inhibiting the tumor ''take'' rate. A similar order of antitumor activity was observed when recombinant adenoviruses were injected intratumorily to previously established PC-3 tumors in vivo. Conclusion: p53 is the most effective tumor suppressor gene to target human prostate cancer.