靶向抑制miR155表达对耐阿霉素多发性骨髓瘤细胞株RPMI8226/DOX耐药性的影响

OBJECTIVE: To explore the mechanism of abnormal expression of microRNA155 (miR155) in myeloma drug-resistance to probe the possibility of inhibiting miR155 expression to restore chemotherapy sensitivity and its molecular mechanism in drug-resistant myeloma cells. METHODS: Drug-resistant myeloma cell-line RPMI8226/DOX was established by culturing RPMI8226 cells with continuous low concentration and intermittent gradually increasing concentration of doxorubicin in vitro; The levels of miR155 mRNA were measured by qRT-PCR, and both proteins FOXO3a and BCL-2 expressions were detected by Western blot in cell-lines RPMI8226/S and RPMI8226/Dox. RPMI8226/DOX cells were transfected by miR155 inhibitor and mimic using gene transfer method, and then CCK-8 was used to measure proliferation and inhibition ratio, the changes of miR155 expression were detected by RT-PCR. Proteins FOXO3a and BCL-2 were detected by Western blot. RESULTS: Comparing with RPMI8226 cells, the level of miR155 mRNA was obviously up-regulated with the relative expression of 26.860±2.340, together with increased expression of Bcl-2 protein but decreased expression of FOXO3a in RPMI8226/DOX cells. After 72 h treatment with miR155 inhibitor, the inhibition rate of transfection was 64.57%, miR155 expression decreased sharply, the level of FOXO3a expression was upregulated while BCL-2 expression decreased, chemotherapy sensitivity was restored on cell-line RPMI8226/DOX with reversed drug-resistance ratio of 2.518. CONCLUSION: The abnormal expression of miR155 was closely associated with myeloma drug-resistance, targeting inhibition of miR155 expression could restore chemotherapy sensitivity by increasing FOXO3a expression in drug-resistant myeloma cells.