Icantly decreased the IC 50 values in cells transfected fa HEK293/ABCB1 tight. However, do not materially impair apatinib Changes the cytotoxicity t of antineoplastic drugs in parental cells. In addition, there was not substantially apatinib Changes the cytotoxicity t of non-ABCB1 or ABCG2 substrates erismodegib LDE225 in sensitive non-MDR cells, or cells on their parents. Apatinib significantly decreased the IC50 values of DOX and paclitaxel compared with ABCB1 inhibitor in MCF-cells and KBv200 7/adr VRP. Similarly apatinib significantly decreased the IC 50 of topotecan compared with ABCG2 inhibitor FTC in S1-80 M1 cells. However, no significant apatinib the sensitivity of drug-sensitive parental cells to antineoplastic drugs has been used in this study.
In addition apatinib had no significant effect on Rev rtsfahren ABCC1-mediated Afatinib EGFR inhibitor resistance to cellular Ren genes ABCC1 lines like HEK293 transfectants KB/ABCC1 and / ABCC1. Therefore, our findings suggest that awareness is clearly ABCB1 or ABCG2 apatinib overexpressing cells with anticancer drugs that are substrates of ABCB1 and ABCG2. Apatinib erh Ht fa Is significant accumulation of DOX and Rho 123 in cells overexpressing ABCB1 and ABCG2 To the mechanism by which the potential apatinib sensitized MDR cells to determine antineoplastic drugs, we examined the effect of apatinib accumulation of DOX and Rho 123 in cells overexpressing ABCB1 or ABCG2. In the absence of apatinib were intracellularly Re concentrations of DOX and Rho 123 low-MDR cells, w During the Erh Increase apatinib fa Is significant intracellular Re accumulation of DOX and Rho 123 in a konzentrationsabh Ngigen way.
The index of DOX apatinib fluorescence in the presence of 0.75, 1.5 and 3 M, was of 1.21, 1.72 and 2.19-fold, respectively in the cells, KBv200 1, 31, 1.86 and 2.44 times and 1.37 respectively in MCF 7/adr, 1.71 and 2.11 times, respectively in S1-80 M1 cells. As shown in Fig. 1B, increased ht Apatinib, 0.75, 1.50 and 3 M, the intracellular Re accumulation of Rho 123 by 1.91, 3.43 and 5.17 times, respectively in the cells KBv200, 1.92, 2.83 and 3.59 times larger he 7/adr than those in MCF and 2.13, 3.42, and 4.16 times, respectively in S1-80 M1 cells. However, not significantly, the intracellular apatinib Re accumulation of DOX and Rho 123 KB in the parental sensitive MCF-7 cells and S1.
It should be noted that S1 M1 80, but not the wild-type ABCG2, overexpress R482G variant, which can transport Rho 123rd Taken together, these results suggest that ABCB1 and ABCG2 apatinib significantly inhibits transport mediated MDR cells. The kinetics of inhibition of DOX efflux ABCB1 or ABCG2 intracellular apatinib To re information on the mechanism of inhibition of ABCB1 and ABCG2 transport apatinib get, we have the effect of the kinetics of intracellular apatinib Ren DOX efflux by ABCB1 or ABCG2 transporter with KBv200 M1 and S1 80 cells. The inhibitory effect of apatinib was determined using Lineweaver Burk in the presence or absence of apatinib. The subsequent End analysis showed that apatinib was a competitive inhibitor of DOX efflux. Ki values for the transport of apatinib ABCB1 and ABCG2 were stimulated by DOX 1.98 and 1.37 0.21 0.17 M. Apatinib the ATPase activity t of ABCB1 and ABCG2 To evaluate the effect apatinib to a