Involvement of the MDR1 gene and glycolipids in anticancer drug-resistance of human ovarian carcinoma-derived cells.

Abstract

We previously reported that anti-paclitaxel-resistant ovarian carcinoma cells characteristically expressed the MDR1 (multidrug resistance 1) gene with enhanced synthesis of glycolipids, i.e., LacCer, Gb3Cer, Leb and GM3, and that anti-cisplatin-resistant cells lost GM3. To further examine the involvement of glycolipids and the MDR1 gene in the anticancer drug-resistance, we determined their expression and the sensitivity to anticancer drugs of several ovarian carcinoma-derived cells, i.e., serous KF28, mucinous HMKOA, endometrioid HNOA and clear cell RMG-1 cells. The MDR1 gene was only detected in RMG-1 cells, in which the amounts of Gb4Cer, Leb and GM3 were higher than in the other cells, which reflected their much higher resistance to paclitaxel and docetaxel compared to the other cells. Among HNOA, HMKOA and KF28 cells, all of which did not express the MDR1 gene, the HNOA and HMKOA cells were relatively more resistant to paclitaxel and docetaxel than KF28 cells, and contained more than sevenfold Gb4Cer and Leb in KF28 cells, indicating that cells containing glycolipids with longer carbohydrate chains, even without expression of the MDR1 gene, have the resistance property as to hydrophobic drugs. On the contrary, RMG-1 cells with the highest amount of GM3 were relatively more sensitive to cisplatin than the other cells, which probably due to a negative charge for binding with cisplatin. Thus, MDR1, and increased amounts of Gb4Cer, Leb and GM3 were suggested to be involved in the anticancer drug-resistance to hydrophobic paclitaxel and docetaxel, and GM3 was to basic cisplatin.