Increase in carcinoembryonic antigen release from cancer cells by combined treatment with retinoic acid and low-temperature hyperthermia.
The growth of a human gastric adenocarcinoma cell line, MKN-45, was inhibited and the amount of carcinoembryonic antigen (CEA) in both the culture medium and the cell extract was increased in the presence of retinoic acid at a concentration of 75 (1.5x)-125 microM (1.9x), which did not substantially affect cell survival. Treatment using a combination of retinoic acid (125 microM) and low-temperature hyperthermia (40 degrees C, 30 min) was more effective in increasing CEA compared with retinoic acid alone (extracellular 1.9-2.4x, intracellular 1.5-1.9x). The inhibition of cell growth was reversed after the retinoic acid was removed from the medium. Cells treated with both retinoic acid and (low-temperature) hyperthermia, however, could be induced to release a significant amount of CEA at about 48 h after retinoic acid removal. The induced CEA increase in the cells, but not in the medium, was suppressed by actinomycin D (1 ng/ml) or cyclohexamide (0.2 microgram/ml). These results suggest that retinoic acid, used alone or in combination with hyperthermia, enhances the production and release of CEA in human gastric cancer cells.
Kobayashi
T
T
Department of Biochemistry, Asia Medical Center, Saitama, Japan.
Dohgome
M
M
Kawakubo
T
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006358:Hot Temperature / Q000627:therapeutic use*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D013696:Temperature; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D003609:Dactinomycin; D014212:Tretinoin; D003513:Cycloheximide