THE ANTIPROLIFERATIVE EFFECT OF PROLIFERATING CELL NUCLEAR ANTIGEN-SPECIFIC ANTISENSE OLIGONUCLEOTIDES ON HUMAN GASTRIC-CANCER CELL-LINES

The proliferating cell nuclear antigen (PCNA) is a nuclear protein tha t leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high prolife rative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in se ven gastric cancer cell lines. It was found that treatment with antise nse oligonucleotides at concentrations of 10-40 mu M dose-dependently inhibited the growth of all cell lines; however, random sequence oligo nucleotides did not modify the proliferation of any type of cells. The se results indicate that PCNA is essential for cell proliferation in g astric cancer cells, and that the growth inhibitory effect results fro m the inhibition of PCNA gene expression. Therefore, PCNA-specific ant isense oligonucleotides may be effective in the treatment of gastric c ancer.