PMID- 11676861 OWN - NLM STAT- MEDLINE DCOM- 20020111 LR - 20190513 IS - 0910-5050 (Print) IS - 1876-4673 (Electronic) IS - 0910-5050 (Linking) VI - 92 IP - 10 DP - 2001 Oct TI - Cyclin D1 antisense oligonucleotide inhibits cell growth stimulated by epidermal growth factor and induces apoptosis of gastric cancer cells. PG - 1102-9 AB - The cyclin D1 protein is one of the cell cycle regulators required for cell cycle progression through G1 phase to S phase. The cyclin D1-cyclin-dependent kinase (CDK) system is thought to control the cell cycle through mediating extracellular signals from mitogens, such as epidermal growth factor (EGF). In this study, we attempted to examine the therapeutic effect of cyclin D1 antisense oligonucleotides (AS/D1) on cell proliferation and apoptosis of the gastric cancer cell line MKN-74, in the presence and absence of EGF-stimulation. Evaluation of cell survival and DNA synthesis revealed that enhanced cell growth following EGF-stimulation was completely inhibited by a 24 h pre-incubation with 100 nM AD/D1. This inhibition was down to 19.3% compared with maximal DNA synthesis after stimulation with 3 nM EGF alone. Western blotting demonstrated that while EGF-stimulation led to cyclin D1 over-expression, AS/D1 inhibited cyclin D1 protein expression. We also demonstrated the induction of apoptosis in MKN-74 cells by AS/D1. In conclusion, EGF-stimulated MKN-74 cell proliferation was inhibited by AS/D1, which could overcome EGF-induced cyclin D1 over-expression. AS/D1 also affected cell survival by inducing apoptosis through cell cycle arrest following cyclin D1 depletion. Thus, AS/D1 may be a candidate for use as a novel cancer therapy specifically targeted against the over-expression of cyclin D1 enhanced by EGF in malignant cells. FAU - Saikawa, Y AU - Saikawa Y AD - Department of Surgery, Hiratsuka City Hospital, Hiratsuka, Kanagawa 254-0065. saikmimi@aol.com FAU - Kubota, T AU - Kubota T FAU - Otani, Y AU - Otani Y FAU - Kitajima, M AU - Kitajima M FAU - Modlin, I M AU - Modlin IM LA - eng PT - Journal Article PL - Japan TA - Jpn J Cancer Res JT - Japanese journal of cancer research : Gann JID - 8509412 RN - 0 (Oligonucleotides, Antisense) RN - 136601-57-5 (Cyclin D1) RN - 62229-50-9 (Epidermal Growth Factor) RN - 9007-49-2 (DNA) SB - IM MH - Apoptosis/*drug effects MH - Blotting, Western MH - Cell Division/drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Cyclin D1/biosynthesis/*genetics/metabolism MH - DNA/biosynthesis MH - Dose-Response Relationship, Drug MH - Epidermal Growth Factor/*pharmacology MH - Humans MH - In Situ Nick-End Labeling MH - Oligonucleotides, Antisense/genetics/*pharmacology MH - Stomach Neoplasms/*pathology MH - Time Factors MH - Tumor Cells, Cultured PMC - PMC5926617 EDAT- 2001/10/26 10:00 MHDA- 2002/01/12 10:01 PMCR- 2001/10/01 CRDT- 2001/10/26 10:00 PHST- 2001/10/26 10:00 [pubmed] PHST- 2002/01/12 10:01 [medline] PHST- 2001/10/26 10:00 [entrez] PHST- 2001/10/01 00:00 [pmc-release] AID - CAE1102 [pii] AID - 10.1111/j.1349-7006.2001.tb01065.x [doi] PST - ppublish SO - Jpn J Cancer Res. 2001 Oct;92(10):1102-9. doi: 10.1111/j.1349-7006.2001.tb01065.x.