Li Li, Jiang Alice C, Dong Pin, Wan Yi, Yu Zi Wei
Department of Otolaryngology, Shanghai Jiao Tong University affiliated First People's Hospital, China.
Otolaryngol Head Neck Surg. 2007 Oct;137(4):659-64. doi: 10.1016/j.otohns.2007.04.026.
To investigate the characteristics of Hep-2 cell with multidrug resistance (MDR) induced by Taxol.
Hep-2 cells were exposed in stepwise escalating concentration of Taxol to develop the resistant cell line-Hep-2T. Cell cycle distribution, apoptosis, and rhodamine accumulation were studied through flow cytometry. The MDR1 and MRP1 genes were detected through real-time quantitative RT-PCR, and the corresponding proteins were detected through Western blotting.
The drug resistance of Hep-2T cells to Taxol, doxorubicin, gemcitabine, 5-FU, and cisplatin all increased. The percentage of G0/G1 phase and the antiapoptosis ability increased significantly compared with Hep-2 cells. Both MDR1 and MRP1 also increased at gene and protein level, though MDR1 was more prominent.
More emphasis should be laid on MDR1/Pgp, the non-Pgp substrate chemotherapeutic agents, and the changes of cell cycle distribution to prevent MDR induced by Taxol.
These findings may provide theoretical support for the reverse of MDR.
研究紫杉醇诱导的多药耐药(MDR)Hep-2细胞的特性。
将Hep-2细胞暴露于逐步递增浓度的紫杉醇中以建立耐药细胞系——Hep-2T。通过流式细胞术研究细胞周期分布、凋亡和罗丹明蓄积情况。通过实时定量逆转录聚合酶链反应(RT-PCR)检测MDR1和MRP1基因,并通过蛋白质印迹法检测相应蛋白。
Hep-2T细胞对紫杉醇、阿霉素、吉西他滨、5-氟尿嘧啶和顺铂的耐药性均增加。与Hep-2细胞相比,G0/G1期百分比和抗凋亡能力显著增加。MDR1和MRP1在基因和蛋白水平均增加,尽管MDR1更为显著。
应更重视MDR1/P-糖蛋白、非P-糖蛋白底物化疗药物以及细胞周期分布的变化,以预防紫杉醇诱导的多药耐药。
这些发现可能为多药耐药的逆转提供理论支持。