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紫杉醇诱导的多药耐药Hep-2细胞的特性

The characteristics of Hep-2 cell with multiple drug resistance induced by Taxol.

作者信息

Li Li, Jiang Alice C, Dong Pin, Wan Yi, Yu Zi Wei

机构信息

Department of Otolaryngology, Shanghai Jiao Tong University affiliated First People's Hospital, China.

出版信息

Otolaryngol Head Neck Surg. 2007 Oct;137(4):659-64. doi: 10.1016/j.otohns.2007.04.026.

Abstract

OBJECTIVE

To investigate the characteristics of Hep-2 cell with multidrug resistance (MDR) induced by Taxol.

STUDY DESIGN

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.

RESULTS

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.

CONCLUSION

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.

SIGNIFICANCE

These findings may provide theoretical support for the reverse of MDR.

摘要

目的

研究紫杉醇诱导的多药耐药(MDR)Hep-2细胞的特性。

研究设计

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。

结果

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。

结论

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。

意义

这些发现可能为多药耐药的逆转提供理论支持。

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