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补肾养骨汤对多发性骨髓瘤细胞株KM3/BTZ多药耐药性的影响

[Effect of Bushen Yanggu Decoction on Multidrug Resistance of Multiple Myeloma Cell Line KM3/BTZ].

作者信息

Li Yu-Peng, Zhang Jian-Guo, Fang Zi-Qing, Huang Xing-Ru, Chen Xu, Li Zhen-Jie, Fang Jian

机构信息

The Third Clinical Medical School of Guangzhou University of Tranditional Chinese Medicine;Guangzhou 510000, Guangdong Province, China.

Department of Orthopedics The Third Affiliated Hospital of Guangzhou University of Tranditional Chinese Medicine;Guangzhou 510000, Guangdong Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Apr;27(2):482-488. doi: 10.19746/j.cnki.issn.1009-2137.2019.02.028.

Abstract

OBJECTIVE

To explore the effect of Bushen Yanggu Decoction (BYD) on drug resistance and proliferation of human multiple myeloma-resistant KM3/BTZ cells.

METHODS

Human multidrug-resistant KM3/BTZ cells were established by Bortezomib (BTZ) gradient induction. The effects of commonly used chemotherapeutic drugs and serum containing Bushen Yanggu Decoction (BYD) on the proliferation of KM3 cells and KM3/BTZ cells were detected by MTT assay. RT-qPCR and Western blot were used to detect the expression of Par-4, HSP27 and P-gp genes. Flow cytometry was used to detect cell apoptosis.

RESULTS

The established KM3/BTZ cells could produce varying degree of resistance to commonly used chemotherapeutic drugs. Among them, the highest resistance index (RI) to BTZ was 20.269. MTT assay showed that the proliferation of KM3/BTZ cells treated with serum containing Bushen Yanggu Decoction was inhibited, and the inhibitory effect increased with the serum concentration incranse of Bushen Yanggu Decoction. The serum containing Bushen Yanggu Decoction could inhibit the proliferation of KM3/BTZ cells, and induce apoptosis, significantly reduce the drug-resistance of KM3/BTZ cells, up-regulate the expression of Par-4, down-regulate the expression of HSP27 and P-gp.

CONCLUSION

Bushen Yanggu Decoction can effectively inhibit the proliferation of KM3/BTZ cells and induce apoptosis. Bushen Yanggu Decoction can effectively reverse the multidrug-resistance of KM3/BTZ cells. The mechanism may be related with the decrease of expression of HSP27 and P-gp and the increase of expression of Par-4.

摘要

目的

探讨补肾养骨汤(BYD)对人多发性骨髓瘤耐药KM3/BTZ细胞耐药性及增殖的影响。

方法

通过硼替佐米(BTZ)梯度诱导建立人多药耐药KM3/BTZ细胞。采用MTT法检测常用化疗药物及含补肾养骨汤血清对KM3细胞和KM3/BTZ细胞增殖的影响。采用RT-qPCR和蛋白质免疫印迹法检测Par-4、HSP27和P-gp基因的表达。采用流式细胞术检测细胞凋亡。

结果

建立的KM3/BTZ细胞对常用化疗药物可产生不同程度的耐药性。其中,对BTZ的最高耐药指数(RI)为20.269。MTT法显示,含补肾养骨汤血清处理的KM3/BTZ细胞增殖受到抑制,且随着补肾养骨汤血清浓度的增加抑制作用增强。含补肾养骨汤血清可抑制KM3/BTZ细胞增殖并诱导凋亡,显著降低KM3/BTZ细胞的耐药性,上调Par-4表达,下调HSP27和P-gp表达。

结论

补肾养骨汤可有效抑制KM3/BTZ细胞增殖并诱导凋亡。补肾养骨汤可有效逆转KM3/BTZ细胞的多药耐药性。其机制可能与HSP27和P-gp表达降低及Par-4表达增加有关。

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