Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts

  • Authors:
    • Toru Shimazui
    • Kazuhiro Yoshikawa
    • Jun Miyazaki
    • Takahiro Kojima
    • Hiromu Inai
    • Satoshi Ando
    • Hirotsugu Uemura
    • Kazuhiko Uchida
    • Hiroyuki Nishiyama
  • View Affiliations

  • Published online on: December 24, 2012     https://doi.org/10.3892/ijo.2012.1752
  • Pages: 543-548
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Abstract

p16INK4a (p16), a key molecule in bladder tumor development, inhibits the activities of cyclin-dependent kinases (CDKs) and maintains the retinoblastoma protein (pRb) in its active hypophosphorylated state. Following the finding that the p16 antitumor peptide dramatically inhibits the growth of aggressive leukemia̸lymphoma through the restoration of p16 function using the Wr-T peptide transporter system, in this study, we developed a systemic therapy using mouse‑p16 peptide (m‑p16) in subcutaneous p16‑null mouse bladder tumors. In vitro analysis showed that the growth of p16‑null bladder tumor cells and the hyperphosphorylation of their pRbs were inhibited by p16 transduction in a concentration‑dependent manner. In an animal model, p16‑null MBT‑2 cells were injected subcutaneously into KSN/SKC nude mice. The systemic delivery of the m‑p16 peptide using Wr‑T by cardiac injection significantly inhibited the growth of solid MBT‑2 tumors compared with the control phosphate‑buffered saline (PBS) injection. Histological examination by TUNEL staining revealed that apoptosis was increased and pRb phosphorylation was inhibited. Thus, the systemic peptide delivery of p16 restores the hypophosphorylation of pRb and may be a useful tool for the treatment of bladder tumors.

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Copy and paste a formatted citation
APA
Shimazui, T., Yoshikawa, K., Miyazaki, J., Kojima, T., Inai, H., Ando, S. ... Nishiyama, H. (2013). Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts. International Journal of Oncology, 42, 543-548. https://doi.org/10.3892/ijo.2012.1752
MLA
Shimazui, T., Yoshikawa, K., Miyazaki, J., Kojima, T., Inai, H., Ando, S., Uemura, H., Uchida, K., Nishiyama, H."Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts". International Journal of Oncology 42.2 (2013): 543-548.
Chicago
Shimazui, T., Yoshikawa, K., Miyazaki, J., Kojima, T., Inai, H., Ando, S., Uemura, H., Uchida, K., Nishiyama, H."Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts". International Journal of Oncology 42, no. 2 (2013): 543-548. https://doi.org/10.3892/ijo.2012.1752