INHIBITION OF GASTRIC-CANCER CELL-PROLIFERATION BY ANTISENSE OLIGONUCLEOTIDES TARGETING THE MESSENGER-RNA ENCODING PROLIFERATING CELL NUCLEAR ANTIGEN

Proliferating cell nuclear antigen (PCNA) is a nuclear protein that re gulates DNA synthesis by DNA polymerase delta, and is essential for DN A replication. PCNA expression level is related to the malignancy of g astric cancer cells. Seven different gastric cancer cell lines and two kinds of control cell lines were treated with antisense oligonucleoti des complementary to the messenger RNA of PCNA. Treatment of each gast ric cancer cell line with antisense oligonucleotides at concentration of 10-40 mu M inhibited the cell growth, colony formation and PCNA pro tein production in a dose-dependent manner, but only affected normal c ells slightly. A random sequence oligomer showed no effect. These resu lts show that PCNA is essential for gastric cancer cell proliferation and that the use of synthetic oligonucleotides is an effective way of producing antisense-mediated changes in the behaviour of human gastric cancers.