Molecular targeting agents have become formidable anticancer weapons, which show much promise against the refractory tumors. Functional peptides are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms a basis for potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. In this report, we examined growth suppression efficiency of human renal carcinomas by peptide targeting system. At first, we analyzed expressions of p16INK4a, p21WAF1 and p27KIP molecules related with RB-Phosphorylation. All of 10 renal cancer cell lines expressed p27 protein, but not p16 protein and 6/10 those cell lines expressed p21 protein. So, We did introduction of two tumor suppressor peptides (p16INK4a and p21WAF1) using Wr-T-mediated peptide delivery system [Mol Cancer Ther 2004;3:1623-30]. Wr-T-mediated transport of both p16INK4a functional peptide into human renal cancer cell lines reversed specific loss of p16 and/or p21 function, thereby drastically inhibiting tumor growth by >90% on 8/10 cell lines and 45-60% on 2/10 cell lines within the first 72 h. Additionally, the combination of p16 and p21 peptides showed more effective activities on 2 cell lines which cell lines were not inhibitted growth activity with p16-single introduction. Then, we investigated the practical effect of Wr-T-mediated p16 MIS delivery on cell cycle-related pRB status. After transduction of functional peptide, phosphorylated pRB (Ser780 phosphorylation) was dramatically decreased in the cells containing Wr-T/ p16 peptide mixture. Wr-T-mediated molecular targeting using antitumor peptides is highly effective against growth of renal cancer cells. Thus, restoring tumor suppressor functions by Wr-T peptide delivery represents a powerful approach, with mechanistic implications for development of efficacious molecular targeting therapeutics against intractable human malignancies.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1711.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009