RRC ID 61503
著者 Kawashima R, Haisa M, Kimura M, Takaoka M, Shirakawa Y, Takeda H, Uetsuka H, Gunduz M, Nagai N, Tanaka N, Naomoto Y.
タイトル Cyclin A correlates with the sensitivity of human cancer cells to cytotoxic effects of 5-FU.
ジャーナル Int J Oncol
Abstract We investigated the role of cyclin A in the cytotoxic effect of 5-fluorouracil (5-FU) on cancer cell lines. Experiments were performed using gastric cancer chemosensitive NUGC3, and chemoresistant NUGC3/5FU/L established by repeated exposure to 5-FU. 5-FU inhibited cell growth of NUGC3 in a dose-dependent manner. Low concentrations of 5-FU did not inhibit cell growth of NUGC3/5FU/L, while high concentrations slightly inhibited cell growth. Examination of the cell cycle pattern of NUGC3 cells showed accumulation at S-phase at 10 micro M and at G1-S-phase at 100 micro M of 5-FU. Cell cycle pattern of NUGC3/5FU/L cells did not change 5-FU concentrations. 5-FU increased cyclin A mRNA level in NUGC3 cells but not NUGC3/5FU/L cells. In the presence of 100 micro M 5-FU, cyclin A protein level increased 2.6-fold in NUGC3 and 1.47-fold in NUGC3/5FU/L. 5-FU dose-dependently increased the percentage of cyclin A-positive NUGC3 cells, but not NUGC3/5FU/L cells. The percentage of cyclin A-positive cells in other 5-FU sensitive esophageal, colon and gastric cancer cell lines (T.Tn, LOVO, DLD-1, MKN-7), increased in the presence of 1 and 10 micro M 5-FU, while cyclin A-positive cells in 5-FU resitant hepatocellular and colon carcinoma cell lines (HCC50 and C-1), did not increase with the same treatment. Our results indicate that the cytotoxic effects of 5-FU in human cancer cell lines correlate with cyclin A and it may be used as a predictive factor for chemotherapy response.
巻・号 24(2)
ページ 273-8
公開日 2004-2-1
PMID 14719102
MeSH Antimetabolites, Antineoplastic / pharmacology Carcinoma, Hepatocellular / drug therapy Cell Line, Tumor Collagen / metabolism Colonic Neoplasms / drug therapy Coloring Agents / pharmacology Cyclin A / biosynthesis* Cyclin A / metabolism Cyclin A / pharmacology Dose-Response Relationship, Drug Flow Cytometry Fluorouracil / pharmacology* Humans Immunoblotting Liver Neoplasms / drug therapy RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction S Phase Tetrazolium Salts / pharmacology Thiazoles / pharmacology Time Factors
IF 3.899
リソース情報
ヒト・動物細胞 MKN7(RCB0999)