title: Possible involvement of glycolipids in anticancer drug resistance of human ovarian serous carcinoma-derived cells.
abstract: Glycolipid and transporter protein gene expression in ovarian serous carcinoma-derived 2008 cells, and their paclitaxel-resistant Px2 and cisplatin-resistant C13 forms was examined to confirm the previous finding, i.e., that it was characteristically altered in anticancer drug-resistant cells established on continuous cultivation of ovarian carcinoma-derived KF28 cells in the different anticancer drug-containing media. Although the concentrations of lipid constituents in 2008 cells were higher than those in KF28 cells, and the glycolipid compositions were different, the following glycolipids and genes were commonly altered in KF28- and 2008-derived resistant cells. Gb(3)Cer was increased in all resistant cells, irrespective of whether the resistance was to paclitaxel or cisplatin, and expression of the MDR1 gene and gangliosides was enhanced in paclitaxel-resistant cells, but gangliosides were absent in cisplatin-resistant cells. In accord with the decreased amounts of gangliosides in cisplatin-resistant cells, the gene expression and specific activity of GM3 synthase were greatly decreased in cisplatin-resistant cells. Furthermore, paclitaxel- and cisplatin-resistant cells were converted to forms more sensitive to the respective anticancer drugs on cultivation with D-PDMP, an inhibitor of GlcCer synthase, and GM3, respectively, prior to the addition of anticancer drugs, indicating the possible involvement of glycolipids in anticancer drug resistance.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Takada
authors.forename: Seiji
authors.initials: S
authors.lastname: Isonishi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
authors.forename: Mikio
authors.initials: M
authors.lastname: Mikami
authors.forename: Kazushige
authors.initials: K
authors.lastname: Kiguchi
authors.forename: Masao
authors.initials: M
authors.lastname: Iwamori
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006017:Glycolipids / Q000378:metabolism / Q000502:physiology*; D016695:Glycosyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D009025:Morpholines / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D012799:Sialyltransferases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002784:Cholesterol; D002945:Cisplatin; D006017:Glycolipids; D016695:Glycosyltransferases; D009025:Morpholines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D010743:Phospholipids; D012799:Sialyltransferases; C033110:RV 538; C021343:haematoside synthetase