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.
Department of Biochemistry, Asia Medical Center, Saitama, Japan.
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Kobayashi
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Dohgome
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Kawakubo
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