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[苦参碱对人鼻咽癌细胞系耐药性的逆转作用]

[Reversal effect of matrine on drug resistance of human nasopharyngeal carcinoma cell line].

作者信息

Zhang Jun, Tang An-Zhou

机构信息

Guangxi Medical University, Nanning 530021, China.

出版信息

Zhong Yao Cai. 2012 Dec;35(12):1989-94.

Abstract

OBJECTIVE

To study the reversal effect of matrine and its derivatives on drug resistance of human nasopharyngeal carcinoma cell line HONE1/DDP.

METHODS

The drug-resistant cell line was established by the human nasopharyngeal carcinoma cells HONE1 with gradually increasing concentration of cisplatin. The matrine and its derivatives were added into the HONE1/DDP according to different concentrations to measure their cytotoxicity. MTT assay was used to measure the reversal effect on the drug resistance of the non-toxic doses of matrine and its derivatives. Cell cycle was measured by flow cytomety. The expression level of MRP1, BAX, BCL-2 was assayed by Western blot.

RESULTS

HONE1/DDP indicated drug resistantance. When the non-toxic doses of matrine and its derivatives were used to HONE1/DDP with 24h, the resistance of HONE1/DDP was down-regulated, the reversal fold was 1.45 and 1.77. The cell number of G0/G1-phase increased in matrine group while S phase decreased in matrine derivatives group compared with HONE1/DDP. Compared with HONE1/DDP group, the MRP1 expression levels in HONE1 cells were reduced (P < 0.05), and Matrine group and matrine derivatives group were enhanced (P < 0.05). The expression of BAX was lower while the expression of BCL-2 was higher.

CONCLUSION

The resistance of HONE1 cells to DDP is able to increase the expression of MRP1; Matrine and its derivatives can reverse the drug resistance of HONE1/DDP to DDP, its activity may be related to change cell cycle distribution, the inhibition of MRP1 expression and down-regulation of BAX/BCL-2.

摘要

目的

研究苦参碱及其衍生物对人鼻咽癌HONE1/DDP细胞株耐药性的逆转作用。

方法

采用逐步增加顺铂浓度的方法,由人鼻咽癌HONE1细胞建立耐药细胞株。将苦参碱及其衍生物按不同浓度加入HONE1/DDP细胞中,检测其细胞毒性。采用MTT法检测苦参碱及其衍生物无毒剂量对耐药性的逆转作用。通过流式细胞术检测细胞周期。采用蛋白质免疫印迹法检测MRP1、BAX、BCL-2的表达水平。

结果

HONE1/DDP呈现耐药性。当苦参碱及其衍生物无毒剂量作用于HONE1/DDP细胞24小时后,HONE1/DDP的耐药性下调,逆转倍数分别为1.45和1.77。与HONE1/DDP组相比,苦参碱组G0/G1期细胞数增加,苦参碱衍生物组S期细胞数减少。与HONE1/DDP组相比,HONE1细胞中MRP1表达水平降低(P<0.05),苦参碱组和苦参碱衍生物组表达增强(P<0.05)。BAX表达较低,而BCL-2表达较高。

结论

HONE1细胞对顺铂的耐药性可使MRP1表达增加;苦参碱及其衍生物可逆转HONE1/DDP对顺铂的耐药性,其作用机制可能与改变细胞周期分布、抑制MRP1表达及下调BAX/BCL-2有关。

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