多柔比星-五味子乙素共载脂质体克服多药耐药的机制研究

目的 探讨多柔比星-五味子乙素共载脂质体克服肿瘤多药耐药机制。方法 制备多柔比星-五味子乙素共载脂质体，以人慢性髓系白血病耐药细胞株K562/DOX为模型细胞，分别探讨不同温度、内吞抑制剂存在下的细胞摄取药物的情况，并检测耐药细胞P-gp表达和细胞凋亡情况。结果 共载脂质体在4℃及氯喹、叠氮钠和甘露醇内吞抑制剂存在下进入耐药细胞的药物量明显减少；流式细胞仪检测多柔比星-五味子乙素共载脂质体可抑制P-gp表达且诱导凋亡。结论 多柔比星-五味子乙素共载脂质体进入K562/DOX细胞主要通过耗能的内吞途径；而多柔比星-五味子乙素共载脂质体克服肿瘤多药耐药可能是通过抑制P-gp表达和促进凋亡双通道途径。

Mechanism Study of Doxorubicin-schisandrin B Co-delivery Liposomes to Overcome Multidrug Resistance

OBJECTIVE To investigate the mechanism of doxorubicin-schisandrin B co-delivery liposomes(DSCL) to overcome multidrug resistance(MDR). METHODS DSCL were prepared. The K562/DOX cells were chosen as the model cells. The low temperature test, Endocytosis inhibitors (chloroquine, sodium azide, and mannitol) test were carried out on K562/DOX cells. And P-gp expression and apoptosis were detected by flow cytometry. RESULTS The uptake of DSCL was energy-dependent and was influenced by temperature, and endocytosis inhibitors, such as chloroquine, sodium azide and mannitol, could decrease significantly accumulation of DOX. The flow cytometry result revealed that the expression of P-gp of K562/DOX cells was significantly inhibited after treatment with DSCL, and it showed DSCL induced a regulated apoptotis in cells. CONCLUSION DSCL were uptaken through the endocytosis of energy-dependent. It is proposed the mechanism of DSCL to overcome multidrug resistance was a dual strategy by inhibiting the expression of P-gp and promoting apoptotis.