Inhibition of pRb phosphorylation and cell cycle progression by an antennapedia-p16(INK4A) fusion peptide in pancreatic cancer cells

In this study, we examined whether or not a small peptide derived from p16( INK4A) protein with the antennapedia carrier sequence could inhibit the gro wth of pancreatic cancer cells through the inhibition of cell cycle progres sion. Growth inhibition by the p16-derived peptide was observed in a time- and dose-dependent manner in AsPC-1 and BxPC-3 cells (p16-negative and pRb- positive), whereas Saos-2 cells (p16-positive and pRb-negative) showed no i nhibitory effect. In AsPC-1 and BxPC-3 cells, the proportion of cells in th e G(1) phase markedly increased 48 h after treatment with 20 muM p16-derive d peptide. Cell-cycle analysis of Saos-2 cells showed little change during the entire period of treatment. Immunoblot analysis showed inhibition of pR b phosphorylation after treatment of BxPC-3 with 10 muM p16 peptide. Furthe rmore, the p16 peptide caused a decrease in cyclin A at later times of trea tment. These results demonstrate that the p16-derived peptide can inhibit t he growth of p16-negative and pRb-positive pancreatic cancer cells by means of G(1) phase cell cycle arrest resulting from the inhibition of pRb phosp horylation. Restoration of p16/pRb tumor-suppressive pathway by re-expressi on of p16(INK4A) may play a therapeutic role in the treatment of pancreatic cancer. (C) 2000 Elsevier Science Ireland Ltd, All rights reserved.