Reversal Effect Of Salinomycin Multidrug-resistance In Renal Cell Carcinoma Line ACHN

Objective: To investigate the reversal effect and mechanism of salinomycin on humanmultidrug resistant (MDR) Renal Cell Carcinoma Line ACHN.Methods:1）Four groups were designed in this experiment: control，adriamycin(ADM),salinomycin(SAL), and adriamycin+salinomycin(combination group)．2）Renal carcinoma cell ACHN were incubated in vitro，the cell activity wasmeasured by CCK-8method at24hours after drug action.Immunocytochemistory was taken to test the expression of P-glycoprotein（P-gp）. The cell cycle distribution was determined by flow cytometry.3）Theresults were analysised by Using SPSS13.0，the data was showed by±s，groups all using two-sample t-test, it has significant difference when p<0.05.Results:1）The growth inhibition rate of10μg/ml adriamycin on ACHN cells was only4.7%. The inhibition rate of salinomycin group presented a dose-dependent,and higher than the adriamycin group (P <0.05), of which10μM salinomycinreached the highest rates (up to17.55%). The growth inhibition rate ofcombination group was higher than salinomycin and adriamycin group (P<0.05), respectively. Among combination group, the growth inhibition rate of10μM adriamycin+10μg/ml salinomycin group was up to45.447%.2）Compared with adriamycin group, expression of P-gp in ACHN cells wasobviously decreased in salinomycin-treated groups （p<0.05）．3） Flowcytometry showed that:the renal cell carcinoma ACHN cells were treatmentby salinomycin,the Go/G1phase cells gradually increased, the cells in Sphase decreased gradually(P <0.05)；The combination group renal carcinomacells in G0/G1phase decreased, the cells in G2/M phase was significantlyincreased (P <0.05). Conclusion: Salinomycin enhanced the sensitivity of renal cell carcinoma ACHN cellsto adriamycin, down-regulated expression of P-gp might be one of themechanisms of multidrug resistance reversal. Salinomycin regulated the cellcycle of the renal cell carcinoma ACHN cells, single application ofsalinomycin caused cell cycle arrest in G0/G1phase, and co-treatment ofdoxorubicin arrested in G2/M phase.