Co-inhibition Of Sorcin And Mdr1 Gene Reverse Multi-drug Resistance Of K562/A02 Cells

Objective:To study the effect of soluble resistance-related calcium-binding protein gene (sorcin) and multidrug resistance gene (mdrl) were inhibited on multi-drug resistance of K562/A02 cells.Methods:An antisense oligodeoxynucleotide(ASODN) targeted sorcin and mdrl were transfected to K562/A02 using Oligofectamine. The expression of sorcin and mdrl were measured using real-time PCR, Western Blot and Flow Cytometry. The sensitivity of cells to doxorubicin(ADR), vincristine(VCR), etoposide(VP-16) and homoharringtonine(HHT) were measured using MTT assay. The affect of sorcin and mdrl transfection on cellular accumulation of cytotoxic agents were measured using Rho123 efflux by FACS analysis. The affect of sorcin and mdrl transfection on cells apoptotic rate were measured using the annexin V/propidium by cytometry.Results:â‘ The expression levels of sorcin and mdrl were obviously reduced by ASODNs(P<0.01);â‘¡Knockdown expression by ASODN of sorcin or mdrl individually significantly reduced K562/A02 cells drug resistance(P< 0.01), simultaneous inhibition of sorcin and mdrl expressions demonstrated stronger degree of reversal of the MDR phenotype(P<0.01);â‘¢Inhibition of mdrl expression could effectively affect cellular accumulation of cytotoxic agents(P<0.01), but sorcin could not seem to significantly, simultaneous inhibition of sorcin and mdrl expressions could effectively affect cellular accumulation of cytotoxic agents(P< 0.01);â‘£Knockdown expression by ASODN of sorcin and mdrl individually significantly enhanced cells apoptotic rate(P< 0.01), simultaneous inhibition of sorcin and mdrl expressions were more higher than individually (P<0.01).Conclusion:â‘ In this study, we used for An antisense oligodeoxynu-cleotide(ASODN) targeted sorcin and mdrl were transfected to K562/A02 using Oligofectamine, that successfully suppressed expression of sorcin and mdrl mRNA and protein levels in the K562/A02 cell lines.â‘¡Knockdown expression by ASODN of sorcin or mdrl individually significantly reduced K562/A02 cells drug resistance, simultaneous inhibition of sorcin and mdrl expressions demonstrated stronger degree of reversal of the MDR phenotype.â‘¢knockdown expression by ASODN of sorcin did not reduced cellular accumulation of cytotoxic agents, but could enhanced cells apoptotic rate; simultaneous inhibition of sorcin and mdrl were not significantly different than inhibition of mdrl with cellular accumulation of cytotoxic agents, but cells apoptotic rate demonstrated higher than individually.â‘£sorcin and mdrl likely represent two independent mechanisms that confer MDR to K562/A02 cells, on the one hand the coexistence of multi-factor phenomenon has been confirmed in multi-drug resistance of cells, on the other hand that could serve as potential targets for therapeutic interv-eneetions of rewersing drug resistance.