Enhanced Cytotoxicity of p27(kip1) Against Cholangiocarcinoma

Strategic Insights -

Investigators in Sendai, Japan have discovered that a new recombinant adenovirus, Adp27-jab-d, expressing a p27(kip1) protein with a deletion of the Jab1-binding region, can induce greater cytotoxicity against human cholangiocarcinoma cells. The Adp27-jab-d virus inhibited the growth of TFK-1 cells in vitro at a concentration 3.3 times lower than its wild-type counterpart, Adp27-wt. In a xenografted SCID mouse model, treatment with Adp27-jab-d once a day for 3 days inhibited tumor growth more strongly than Adp27-wt or Adp27-mt and even induced tumor regression.

Key Takeaways:

  • The p27(kip1) protein, a negative regulator of cell cycling, has antitumor effects and is a tumor suppressor gene like p53.
  • The p27(kip1) protein binding with Jab1 leads to its degradation by the 26S proteasome system, but a deletion of the Jab1-binding region increases its protein stability.
  • The Adp27-jab-d virus is a recombinant adenovirus that expresses a p27(kip1) protein with a deletion of the Jab1-binding region, which increases its cytotoxicity against cholangiocarcinoma cells.
  • The Adp27-jab-d virus inhibited the growth of TFK-1 cells in vitro at a concentration 3.3 times lower than Adp27-wt.
  • In a xenografted SCID mouse model, treatment with Adp27-jab-d once a day for 3 days inhibited tumor growth more strongly than Adp27-wt or Adp27-mt and even induced tumor regression.
  • The mechanism of actions of Adp27-jab-d involves not only apoptosis but also necrosis, which is a specific effect of the virus.

Statistics:

  • The Adp27-jab-d virus inhibited the growth of TFK-1 cells in vitro at a concentration 3.3 times lower than Adp27-wt.
  • The Adp27-jab-d virus induced tumor regression in a xenografted SCID mouse model.
  • The flow cytometric TUNEL assay showed little enhancement of apoptosis, indicating that Adp27-jab-d also causes necrosis.

Sources:

  • Overexpression of Adenovirus-mediated p27(Kip1) Lacking the Jab1-binding Region Enhances Cytotoxicity and Inhibits Xenografted Human Cholangiocarcinoma Growth. Anticancer Research, 2009;29(6):2015-2024.
  • Tohoku University, Medical Department.
  • International Institute Anticancer Research, Editorial Office 1ST km Kapandritiou-Kalamou Rd. Kapandriti, PO Box 22, Athens 19014, Greece.