Optimization of chemotherapy of ovarian cancer as an indicator of transporter expression and glycolipid

为了进一步研究人卵巢癌抗癌耐药性的分子基础，我们比较了浆液性卵巢癌2008细胞与紫杉醇耐药的Px2和顺铂耐药的C13细胞。尽管耐药细胞中的主要脂质，即胆固醇、神经酰胺和磷脂的含量与敏感细胞中的相同，但Gb3Cer在耐药细胞中显著增加，无论耐药的是紫杉醇还是顺铂。此外，神经节苷脂GM1和GD1a在紫杉醇耐药细胞中增加，但在顺铂耐药细胞中缺失。紫杉醇耐药细胞mdr1基因表达明显增强。因此，转运蛋白和糖脂的共表达可通过糖脂与生物膜筏结构中蛋白质之间的氢键加强分子堆积来提高转运蛋白的活性。

To further characterize the molecular basis on anticancer drug-resistance of human ovarian carcinoma, we compared serous ovarian carcinoma derived 2008 cells with the taxol-resistant Px2 and cisplatin-resistant C13 cells. Although the amounts of major lipids, i.e. cholesterol, ceramides and phospholipids, in the resistant cells were same with those in the sensitive cells, Gb3Cer was characteristically increased in the resistant cells, irrespective of whether the resistance was to taxol or cisplatin. Also, gangliosides GM1 and GD1a were increased in the taxol-resistant cells, but were absent in the cisplatin-resistant cells. Expression of MDR1 gene was significantly enhanced in the taxol-resistant cells. Thus, coexpression of transporter proteins and glycolipids was suggested to enhance the activity of transporter proteins by strengthening the molecular packing through the hydrogen bonds between glycolipids and proteins in the raft structures of biomembrane.