Glutathione peroxidase 3 is a candidate mechanism of anticancer drug resistance of ovarian clear cell adenocarcinoma

Abstract

Ovarian clear cell adenocarcinoma has low sensitivity to platinum drugs. The molecular-biological mechanism of the low sensitivity has not been clarified. The objective of this study was to identify candidate genes associated with low sensitivity of clear cell adenocarcinoma to platinum drugs. Exhaustive gene profiling of 4 ovarian clear cell adenocarcinoma cell lines, KK, OVMANA, OVSAYO, and RMG-1 and 4 ovarian serous adenocarcinoma cell lines, KF, HRA, SHIN-3 and KOC-2S was performed by DNA microarray. Obtained candidate genes were suppressed by RNA interference and changes in the cisplatin sensitivity of clear cell adenocarcinoma cells were observed. Six genes including the glutathione peroxidase 3 (GPX3) gene were identified to be highly expressed in clear cell adenocarcinoma by DNA microarray analysis. GPX3 suppression by RNA interference increased cisplatin sensitivity 3.3-4.2-fold in 3 of the 4 clear cell adenocarcinoma cell lines. GPX3 was identified to be a gene highly expressed in clear cell adenocarcinoma. Since GPX3 suppression increased the cisplatin sensitivity of clear cell adenocarcinoma cells, GPX3 may be a candidate gene associated with the low cisplatin sensitivity of clear cell adenocarcinoma.