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[反义硫代磷酸酯寡核苷酸逆转人肝癌耐药细胞SMMC-7721/ADM的多药耐药基因MDR1和MRP]

[Reversal of multidrug resistance gene MDR1 and MRP of drug-resistant human hepatocellular carcinoma cells SMMC-7721/ADM with antisense phosphorothioate oligonucleotides].

作者信息

Luo Hua-you, Yang Jia-yin, Liu Zi-ming, Lin Qi-yuan, Yan Lu-nan

机构信息

Department of General Surgery, the First Affiliated Hospital, West China University of Medical Science, Chengdu 610041, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2004 Feb;12(2):85-7.

PMID:14980107
Abstract

OBJECTIVES

To investigate the reversal effect of gene MDR1 and MRP with combinational antisense phosphorothioate oligonucleotide on Drug-resistant human hepatocellular carcinoma cells SMMC-7721/ADM.

METHODS

SMMC-7721/ADM was transfected with synthetic antisense phosphorothioate oligonucleotides complementary to gene MDR1 and MRP mediated by Lipofectamine. Drug sensitivity was measured by MTT assay, Fluorescence intensity of cells was determined by flow cytometric analysis, RH123 and DNR retention was assayed by confocal scanning laser microscopy.

RESULTS

ASODN of MDR1+MRP increased the sensitivity of SMMC-7721/ADM to chemotherapeutic drug more significantly than that any of MDR1 and MRP did separately. But they did not enhance the inhibition expression of protein of p190 or p170.

CONCLUSION

Drug-resistance could be reversed significantly when antisense phosphorothioate oligonucleotide of MDR1+MRP were transfected into drug-resistant human hepatocellular carcinoma cells SMMC-7721/ADM together.

摘要

目的

探讨基因MDR1和MRP的组合反义硫代磷酸酯寡核苷酸对耐药人肝癌细胞SMMC-7721/ADM的逆转作用。

方法

用脂质体介导的与基因MDR1和MRP互补的合成反义硫代磷酸酯寡核苷酸转染SMMC-7721/ADM。采用MTT法检测药物敏感性,流式细胞术分析细胞荧光强度,共聚焦扫描激光显微镜检测RH123和DNR潴留情况。

结果

MDR1+MRP的反义寡核苷酸(ASODN)比单独的MDR1和MRP更显著地增加了SMMC-7721/ADM对化疗药物的敏感性。但它们并未增强p190或p170蛋白的抑制表达。

结论

将MDR1+MRP的反义硫代磷酸酯寡核苷酸共同转染到耐药人肝癌细胞SMMC-7721/ADM中可显著逆转耐药性。

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