Effect of EPA on Hsp90 and GRα protein expression in multiple myeloma drug-resistant cells.

Abstract

BACKGROUND:

Approximately 20% of MM patients harbor glucocorticoid (GC) resistance and are not responsive to therapeutic effect. Chaperoneheat-shock proteins Hsp90 is needed for ligand docking, The imbalance of Hsp90/GRα (glucocorticoid receptor α) may be an important cause of GC resistance. Recent studies have indicated that EPA could repress cancer cell growth by regulating critical influential factors in progression of cancer, consisting of resistance to drugs, chemosensitivity. The aim of the present study was to test the cytotoxic effects of EPA alone or EPA + Dexamethasone in dexamethasone-resistant MM cell (MM.1R) and investigate whether DHA can induce apoptosis and reverse acquired glucocorticoid resistance in dexamethasone-resistant MM cell (MM.1R).

METHODS:

Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of MM.1R cells after treating with EPA alone and EPA combined with DEX. Mitochondrial membrane potential was measured by flow cytometry and GRα and Hsp90 protein expression were assessed by western blot analysis.

RESULTS:

EPA alone was able to inhibit cell proliferation as evidenced by CCK-8 assay and the tumor growth was remarkably suppressed by EPA + Dexamethasone, Cell apoptosis after EPA treatment was obviously observed by Flow cytometry analysis of the mitochondrial membrane potential. Analysis of Hsp90 and GRα proteins in MM.1R cells incubated with EPA revealed down-regulation of Hsp90 and up-regulation of GRα. Accordingly, the Hsp90/GRα ratio was significantly decreased with the increase of EPA concentration.

CONCLUSIONS:

EPA might be used as a new effective treatment for reversal of glucocorticoid-resistance in multiple myeloma.

• Authors: Shenghao Wu, Yuemiao Chen, Xueshuang Wang, Shanshan Weng, Wenjin Zhou, Zhen Liu
• Journal: BMC cancer (BMC Cancer) Vol. 21 Issue 1 Pg. 1076 (Oct 03 2021) ISSN: 1471-2407 [Electronic] England
• PMID: 34600510 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Cryoprotective Agents
• Glucocorticoids
• HSP90 Heat-Shock Proteins
• Receptors, Glucocorticoid
• glucocorticoid receptor alpha
• Docosahexaenoic Acids
• Dexamethasone
• Eicosapentaenoic Acid
• Dimethyl Sulfoxide

Topics

• Apoptosis (drug effects)
• Cell Culture Techniques
• Cell Proliferation (drug effects)
• Cryoprotective Agents (pharmacology)
• Dexamethasone (pharmacology)
• Dimethyl Sulfoxide (pharmacology)
• Docosahexaenoic Acids (pharmacology)
• Drug Resistance, Neoplasm (drug effects, physiology)
• Eicosapentaenoic Acid (pharmacology)
• Glucocorticoids (pharmacology)
• HSP90 Heat-Shock Proteins (metabolism)
• Humans
• Membrane Potential, Mitochondrial (physiology)
• Multiple Myeloma (drug therapy, pathology)
• Receptors, Glucocorticoid (metabolism)