The effects of the adenovirus-mediated wild-type p53 delivery in human epithelial ovarian cancer cell line in vitro and in vivo.

Abstract

Hwang ES, Kim J, Kim JS, Kao C, Ko S-C, Chung L, Lee J-H. The effects of the adenovirus-mediated wild-type p53 delivery in human epithelial ovarian cancer cell lines in vitro and in vivo. Int J Gynecol Cancer 1998; 8: 27-36. The effect of p53 overexpression on the proliferation of various ovarian cancer cell lines was tested by using an adenovirus vector, Avp53, that expresses wild-type human p53. Cell lines SKOV3, 2774, and OVCAR3, which bear mutations in the endogenous p53 gene, were all affected by Avp53 treatment, undergoing growth suppression and apoptosis at a dose that had little effect on the growth of normal fibroblasts. In these cells, p21WAF1/CIP1 was readily induced and the hypophosphorylated pRb protein accumulated by the treatment of Avp53, suggesting that the growth inhibitory pathway can be activated in these cells by the expression of wild-type p53. However, in PA-1 cell line which endogenously expresses wild-type p53, p21WAF1/CIP1 was not induced by p53 transduction, although p53 was found transcriptionally active. These results indicate that the tested ovarian cancer cell lines bear defects either in p53 itself or in the responsiveness to p53. The cytocidal effect of Avp53 was also examined in vivo against tumors developed in the peritoneal cavity of nude mice. Avp53 administered intraperitoneally eradicated microscopic and small-sized tumor nodules, demonstrating that the intraperitoneal administration of Avp53 may serve as an effective adjuvant therapy for ovarian cancers.