Targeting miR155 restores chemotherapy sensitivity in drug-resistant myeloma cell-line RPMI8226/DOX cells

• Published in: Zhōnghuá xuèyèxué zázhì 2017-01, Vol.38 (1), p.55-59
• Main Authors: Xiao, C R, Hong, X L, Hu, J S, Chen, Y M, Lu, Q Y
• Format: Article
• Language: Chinese
• Subjects: Cell Line, Tumor; Drug Resistance, Neoplasm; Humans; MicroRNAs; Multiple Myeloma; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger
• ISSN: 0253-2727
• DOI: 10.3760/cma.j.issn.0253-2727.2017.01.012

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. Drug-resistant myeloma cell-line RPMI8226/DOX was established by culturing RPMI8226 cells with continuous low concentration and intermittent gradually increasing concentration of doxorubicin ; 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. 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. 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.