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

为了进一步表征人卵巢癌耐药的分子基础，我们将浆液性卵巢癌来源的2008细胞与紫杉醇耐药Px2和顺铂耐药C13细胞进行了比较。尽管耐药细胞中主要脂质（胆固醇、神经酰胺和磷脂）的含量与敏感细胞相同，但无论对紫杉醇还是顺铂耐药，在耐药细胞中Gb3Cer均显著升高。神经节苷类GM1和GD1a在紫杉醇耐药细胞中升高，而在顺铂耐药细胞中不存在。MDR1基因在紫杉醇耐药细胞中的表达显著增强。因此，转运蛋白和糖脂的共表达可以通过糖脂和蛋白质之间的氢键在生物膜的筏状结构中加强分子包装，从而增强转运蛋白的活性。

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.