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

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/GR alpha (glucocorticoid receptor alpha) 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 GR alpha 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 GR alpha proteins in MM.1R cells incubated with EPA revealed down-regulation of Hsp90 and up-regulation of GR alpha. Accordingly, the Hsp90/GR alpha 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.

Automated summary

This study found that EPA can inhibit cell proliferation, induce apoptosis, and regulate Hsp90 and GR alpha protein expression, potentially offering a new effective treatment for reversal of glucocorticoid-resistance in multiple myeloma.