Mechanism of bortezomib resistance induced by HSP27 in multiple myeloma cells

doi:10.3877/cma.j.issn.1674-0785.2021.10.011

Abstract

Abstract:

Objective

To investigate the mechanism of heat shock proteins 27 (HSP27) induced bortezomib (BTZ) resistance in multiple myeloma (MM) cell line U266.

Methods

Drug-resistant cell strain U266/BTZ was induced by treatment with increasing concentrations of BTZ, and drug resistance was detected by CCK8 method. The expression of HSP27 in U266 and U266/BTZ cells before and post BTZ treatment was detected by real-time fluorescence quantitative PCR (RT-PCR) and Western blot. Hsp27-siRNA was used to interfere with the expression of HSP27 in U266/BTZ cells, and then RT-PCR and Western blot were used to identify the effects of HSP27-siRNA interference on apoptosis and endoplasmic reticulum stress, as well as the expression of cl-Caspase-3, cl-Caspase-8, and cl-Caspase-9.

Results

CCK8 assay showed that U266/BTZ cells had reduced drug resistance to many drugs. BTZ exposure significantly upregulated the expression of HSP27 mRNA and protein in U266 and U266/BTZ cells (P＜0.01). Hsp27-siRNA interference significantly down-regulated the expression of HSP27. Hsp27-siRNA interference could enhance the apoptosis of U266/BTZ cells and increase the activation of Caspase-3, Caspase-8 and Caspase-9 (P＜0.01).

Conclusion

HSP27-mediated MM resistance is caused by inhibition of endoplasmic network stress to reduce myeloma cell apoptosis.

Key words: Multiple myeloma, U266 cell line, Heat shock proteins 27, Bortezomib, Drug resistance

Jie Su, Xiaojing Yang, Xue Zhou. Mechanism of bortezomib resistance induced by HSP27 in multiple myeloma cells[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(10): 779-784.

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URL: https://zhlcyszz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0785.2021.10.011

https://zhlcyszz.cma-cmc.com.cn/EN/Y2021/V15/I10/779

Figures/Tables 5

References 17

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项目	BTZ	DOX	ET
U266细胞	15.93±3.56	0.31±0.05	16.27±2.39
U266/BTZ	153.95±23.91	1.93±0.22	61.19±7.39
t值	5.492	4.261	4.112
P值	＜0.001	0.001	0.001

项目	BTZ	DOX	ET
U266细胞	15.93±3.56	0.31±0.05	16.27±2.39
U266/BTZ	153.95±23.91	1.93±0.22	61.19±7.39
t值	5.492	4.261	4.112
P值	＜0.001	0.001	0.001

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