Combination Effect of MicroRNA-15a and MicroRNA- 16-1 on Chemosensitivity of the Leukemia Cells

Background: down-regulation of mirna-15a and mirna-16-1 is associated with bcl-2 and mcl- 1 expression and chemoresistance in tumor cells. in this study, the combined effect of mirna-15a and mirna-16-1 on apoptosis and sensitivity of the chronic lymphocytic leukemia (cll) cells to fludarabine and abt-199 was investigated. materials and methods: the experiment groups were as follows: abt-199, negative control (nc) mirna, mirna-15a, mirna-16, mirna-15a+mirna-16, nc mirna+abt-199, mirna- 15a+mirna-16+abt-199, erlotinib blank control, mirna blank control and combination blank control. the expression levels of bcl-2 and mcl-1 were measured using quantitative real-time pcr (qrt-pcr). the effect of treatments on cell growth and survival was measured by trypan blue staining and mtt (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide) assay, respectively. apoptosis was measured using caspase-3 activity and elisa cell death assays. results: transfection of mirna-15a or mirna-16-1 significantly suppressed the expression of bcl-2 and mcl-1 in a time-dependent manner (p<0.05 versus negative control mirna or blank control). other experiments showed that up-regulation of mirna-15a or mirna-16-1 decreased cell growth, induced apoptosis, and synergistically lowered the ic_50 value of fludarabine and abt-199 in cll cells. moreover, co-transfection of two mirnas showed a more significant effect on cell survival, apoptosis, and drug sensitivity than single transfection. conclusion: our study shows that mirna-15a and mirna-16-1 can effectively enhance the anticancer effects of fludarabine and abt-199 in cll cells and may offer a new promising therapeutic strategy for cll-resistant patients.