Bcl-2 in cancer and normal tissue cells as a prediction marker of response to 5-fluorouracil.
Bcl-2 in cancer cells was shown to be a potent indicator of 5-FU efficacy, but the protein in normal tissue cells appeared not to be a marker of 5-FU toxicity probably due to the functional alteration of Bcl-2 associated with cell senescence. Transfection analysis of Bcl-2-S and Bcl-2-AS into A549 lung cancer cells revealed that Bcl-2 suppressed cell death induced by 5-FU, and the gene expression level of Bcl-2 was closely correlated with the IC50 for 5-FU in 21 fresh human gastric tumor specimens. Such correlation could not be observed in a neonatal human foreskin fibroblast strain, MJ90 (HCA2), and 21 human normal tissues adjacent to tumors. Transfection analysis of Bcl-2-S and Bcl-2-AS into MJ90 cells showed that Bcl-2 correlated with the resistance to 5-FU in the transfectants at PDL60 as in A549 cells, but increased Bcl-2 in the PDL72 senescent transfectant did not cause an increase of the resistance to 5-FU. Cell aging was observed in MJ90 cells and Bcl-2 in the cells was found to decrease with the cell senescence. The senescent cells, however, were more resistant to 5-FU than the younger PDL60 cells having proliferation activity.
Sasaki
Masao
M
Department of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
Kumazaki
Tsutomu
T
Tanimoto
Keiji
K
Nishiyama
Masahiko
M
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015415:Biomarkers; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000502:physiology; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D005472:Fluorouracil