Glutathione peroxidase 3 is a candidate mechanism of anticancer drug resistance of ovarian clear cell adenocarcinoma.
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.
Saga
Yasushi
Y
Department of Obstetrics and Gynecology, Jichi Medical University, Tochigi 329-0498, Japan. saga@jichi.ac.jp
Ohwada
Michitaka
M
Suzuki
Mitsuaki
M
Konno
Ryo
R
Kigawa
Junzo
J
Ueno
Shuichi
S
Mano
Hiroyuki
H
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy* / Q000201:enzymology; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003124:Colorimetry / Q000379:methods; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase; D002945:Cisplatin