COX-2 has major roles in inflammatory reaction, and COX-2 inhibitor and genistein have a chemopre-ventive effect on some cancers such as colorectal, breast, and prostate cancer (PCa). The aims of this study was to investigate combined effect of COX-2 inhibition and genistein treatment. To address this issue, we tested the degree of cell survival and the changes of androgen receptor in PCa cells with silencing of COX-2 according to concentrations of genistein. DU-145 PCa cells were transfected with COX-2 siRNA. The mRNA expressions of androgen receptor and caspase-3 were detected using reverse transcription polymerase chain reaction in the cells with or without COX-2 siRNA transfection. Immunofluorescent staining was performed on PCa cell with COX-2, androgen receptor and caspase-3 antibody and analyzed with confocal microscopy and image analyzer. Cell cytotoxicity according to concentrations of genistein was analyzed with MTT assay. The mRNA expression of AR was down-regulated in DU-145 cell line according to concentration of gen-istein, but caspase-3 expression showed up-regulated pattern in increasing the dosage of genistein. COX-2 siRNA (+) group was stronger mRNA expression of caspase-3 and weaker mRNA expression of AR than COX-2 siRNA (-) group. The immunofluorescent staining results were similar with those of mRNA expression. The results of cell survival showed that COX-2 siRNA (+) group with genistein was more cytotoxic compared to COX-2 siRNA (-) group (Repeated Measured ANOVA, p=0.004). There was significant cytotoxic effects in COX-2 siRNA (+) group between 10μM and 50μM of concentration of genistein compared to COX-2 siRNA (-) group (p<0.0001). The effect of genistein and silencing of COX-2 shows that it reduced AR and increased caspase-3 in PCa cells. These results suggest that genistein and silencing of COX-2 might be a role in the inhibition of cell proliferation and induction of apoptosis.
|ジャーナル||Journal of the Faculty of Agriculture, Kyushu University|
|出版ステータス||出版済み - 8月 1 2014|
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