Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line

Aim:  To determine the receptor subtypes of melatoninin estrogen receptor-positive endometrial cancer cell line, Ishikawa, and the influence of melatoninon chemosensitivity. Methods:  To confirm the subtype of melatoninon Ishikawa cells, cells were treated with melatoninalone and with antagonists against melatonin receptor luzindoleand 4-phenyl-2-propionamidotetralin (4-P-PDOT). Expression of MT1/MT2 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemistryof MT1/MT2 was also performed. The effect of melatoninagainst expression of MT1, MT2, and ERα-receptors mRNA was compared with RT-PCR. To determine whether melatoninenhances the effect of anticancer agents, chemosensitivitytest was performed with or without melatonin. Results:  Our study revealed that Ishikawa cells express MT1 by both RT-PCR and immunocytochemistry. In contrast, expression of MT2 mRNA was not found. Furthermore, ERα mRNA expression was attenuated at melatoninlevel of 1 × 10−9 M. Chemosensitivitytest revealed that melatoninenhanced anti-tumor effects of paclitaxel among anticancer drugs tested. Conclusion:  Based on the above results, MT1 receptor, but not MT2, is expressed in Ishikawa cells. It was also revealed that the cytostatic effect of melatoninis partly an action mediated by MT1 receptor, and attenuation of ERα expression was predicted as the mechanism of action. Clinical application of melatoninto biochemotherapy might be also expected.