The anti-proliferative 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 that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative 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 seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10-40 microM dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.
Sakakura
C
C
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Hagiwara
A
A
Tsujimoto
H
H
Ozaki
K
K
Sakakibara
T
T
Oyama
T
T
Ogaki
M
M
Takahashi
T
T
D001483:Base Sequence; D002455:Cell Division; D004247:DNA / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA