title: A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system.
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 p16INK4a 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.
authors.affiliation: Department of Urology, Aichi Medical University School of Medicine, Nagakute, 480-1195 Aichi, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Zennami
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Kogenta
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Upsilonamada
authors.forename: Marco A
authors.initials: MA
authors.lastname: De Velasco
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
authors.forename: Toru
authors.initials: T
authors.lastname: Shimazui
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Saga
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Honda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003543:Cysteamine / Q000031:analogs & derivatives; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D026901:Membrane Transport Proteins / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy / Q000379:methods*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D023041:Xenograft Model Antitumor Assays
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D026901:Membrane Transport Proteins; C503924:Pep-1 peptide; D010455:Peptides; D003543:Cysteamine