Effect Of Sildenafil Homologues On Drug Resistance In Human Breast Cancer Cell Line MCF-7/ADR

Tumor MDR is the main reason for cancer chemotherapy failure and patients death.Research of the non-toxic reversal agents is an exploratory research for reversing tumorMDR. To explore the reversal effect of XDNF1-0425and XDNF8-0113on Doxorubicinresistance in human breast cancer cell line MCF-7/ADR in vitro.In human breast cancercell line MCF-7/ADR,MTT assay was used to determine the cell growth inhibiting ratio ofboth cells by Sildenafil/XDNF1-0425/XDNF8-0113/Doxorubici （DOX）/Doxorubici（DOX）+Sildenafil homologues.Further more,figured out each inhibitive concentration50(IC50) of DOX. Taking untreated MCF-7/ADR as controls,flow cytometry was applied todetect the intracellular concentration of rhodamine123in MCF-7/ADR cell intervened withXDNF1-0425or XDNF8-0113in order to analyse the its effect on P-gp mediated drugefflux. The expression of P-gp was determined with RT—PCR or western blot．UseGENMED phosphodiesterase5(PDE5) activityassay kit to detect the inhibition of Twokinds ofsildenafil homologues for PDE5.The sensiticity of MCF-7/ADR to DOX wassignificantly increase by XDNF1-0425and XDNF1-0113in a dose-dependentmanner(P<0.05).On one hand,the sensiticity of MCF-7/ADR to DOX was significantlyincrease by10μmol/L or20μmol/L XDNF1-0425with a reversal fold of6.36/11.83. On theother hand,the sensiticity of MCF-7/ADR to DOX was significantly increase by10μmol/Lor20μmol/LXDNF1-0113with a reversal fold of5.58/13.47.The fluorescence intensity ofSildenafil homologues-treated cells were significantly higher than that of the controls, whenat the concentration of10μmol/L or20μmol/L.SPA results showed that two kinds ofhomologues which compared with sildenafil have weaker inhibitory activity of PDE5. Certain concentration of XDNF1-0425and XDNF1-0113can blocking the function of P-gpmediated drug efflux and effectively reverse Doxorubicin resistance in human breast cancercell line MCF-7/ADR in vitro.