A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system

Kenji Zennami, Kazuhiro Yoshikawa, Eisaku Kondo, Kogenta Nakamura, Yoshiaki Yamada, Marco A. De Velasco, Motoyoshi Tanaka, Hirotsugu Uemura, Toru Shimazui, Hideyuki Akaza, Shinsuke Saga, Ryuzo Ueda, Nobuaki Honda

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16 INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96 h. In vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.

Original languageEnglish
Pages (from-to)327-333
Number of pages7
JournalOncology reports
Volume26
Issue number2
DOIs
Publication statusPublished - 01-08-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Zennami, K., Yoshikawa, K., Kondo, E., Nakamura, K., Yamada, Y., De Velasco, M. A., Tanaka, M., Uemura, H., Shimazui, T., Akaza, H., Saga, S., Ueda, R., & Honda, N. (2011). A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system. Oncology reports, 26(2), 327-333. https://doi.org/10.3892/or.2011.1290