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: Kyoko Tanaka, Hidetaka Takada, Seiji Isonishi, Daisuke Aoki, Mikio Mikami, Kazushige Kiguchi, Masao Iwamori
• Journal: Journal of biochemistry (J Biochem) Vol. 152 Issue 6 Pg. 587-94 (Dec 2012) ISSN: 1756-2651 [Electronic] England
• PMID: 23038675 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Glycolipids
• Morpholines
• Multidrug Resistance-Associated Proteins
• Phospholipids
• RV 538
• Cholesterol
• Glycosyltransferases
• Sialyltransferases
• haematoside synthetase
• Paclitaxel
• Cisplatin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinoma (drug therapy)
• Cell Line, Tumor (drug effects)
• Cell Survival (drug effects)
• Cholesterol (metabolism)
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm
• Female
• Glycolipids (metabolism, physiology)
• Glycosyltransferases (genetics, metabolism)
• Humans
• Inhibitory Concentration 50
• Morpholines (pharmacology)
• Multidrug Resistance-Associated Proteins (genetics, metabolism)
• Ovarian Neoplasms (drug therapy)
• Paclitaxel (pharmacology)
• Phospholipids (metabolism)
• Sialyltransferases (metabolism)