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Nrf2的下调增强了奥沙利铂对H460细胞的细胞毒性

[Down-regulation of Nrf2 enhances the cytotoxicity of Oxaliplatin to H460 cells].

作者信息

Xin Ai, Ren Hua-yu, Tang Xiu-wen

机构信息

Department of Biochemistry and Genetics, College of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2010 Jan;39(1):11-6. doi: 10.3785/j.issn.1008-9292.2010.01.003.

Abstract

OBJECTIVE

To establish a stable H460 cell line with Nrf2 down-regulation to study the role of Nrf2 in Oxaliplatin resistance.

METHODS

Nrf2 down-regulated H460 cell line was obtained by transfecting cells with pRS-hNrf2 and followed by screening for Nrf2 expression by Western blotting. The cell lines were further characterized by analysing cellular GSH levels and cytotoxicity to anti-cancer drugs with MTS.

RESULT

Nrf2 down-regulated H460 cell lines were established successfully. Cellular GSH level reduced significantly in the H460-C9 and H460-C13 compared to control cells (P(C9)= 0.00249, P(C13)= 0.03944). Down-regulation of Nrf2 in H460 sensitized the anti-cancer effect of Oxaliplatin and Doxorubicin.

CONCLUSION

Nrf2 plays an important role in drug resistance. Down regulation of Nrf2 in H460 cell enhances cytotoxicity of Oxaliplatin.

摘要

目的

建立Nrf2表达下调的稳定H460细胞系,以研究Nrf2在奥沙利铂耐药中的作用。

方法

用pRS-hNrf2转染细胞,通过蛋白质免疫印迹法筛选Nrf2表达,从而获得Nrf2表达下调的H460细胞系。通过分析细胞内谷胱甘肽(GSH)水平以及用MTS法检测细胞对抗癌药物的细胞毒性,对细胞系进行进一步鉴定。

结果

成功建立了Nrf2表达下调的H460细胞系。与对照细胞相比,H460-C9和H460-C13细胞内的GSH水平显著降低(P(C9)=0.00249,P(C13)=0.03944)。H460细胞中Nrf2的下调增强了奥沙利铂和阿霉素的抗癌效果。

结论

Nrf2在耐药中起重要作用。H460细胞中Nrf2的下调增强了奥沙利铂的细胞毒性。

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