Increase in carcinoembryonic antigen release from cancer cells by combined treatment with retinoic acid and low-temperature hyperthermia

Abstract

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 (1ċ5×)-125 μM (1ċ9×), which did not substantially affect cell survival. Treatment using a combination of retinoic acid (125 μM) and low-temperature hyperthermia (40°C, 30 min) was more effective in increasing CEA compared with retinoic acid alone (extracellular 1ċ9-2ċ4×, intracellular 1ċ5-1ċ9×). 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 (0-2μg/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.

Key Words:

• CEA release
• combination of vitamin A and low-temperature hyperthermia