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

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

来源：Oncology Reports, 2011, 26(2): 327-333.

DOI：10.3892/or.2011.1290

• PTD
• p16
• renal cell carcinoma

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 p16(INK4a) 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 p16(INK4a) 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 p16(INK4a) peptide alone, however, inoculation of Wr-T and the p16(INK4a) a 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.

• 出版日期2011-8