Modulation of MDR in MDR cell lines by crizotinib The IC50 values of the anticancer drugs in resistant and sensitive cells in the absence or presence of crizotinib are shown in Table 1. Crizotinib produced a concentration PF299804 solubility dependent decline in the values of doxorubicin and paclitaxel in KBv200 cells and MCF 7/adr cells but didn’t alter the cytotoxicity of cisplatin, which can be not an ABCB1 substrate. Furthermore, crizotinib notably decreased the IC50 values of doxorubicin and paclitaxel in stably transfected HEK293/ABCB1 cells. However, no development effects of crizotinib were observed in the adult cells. Additionally, crizotinib had no significant change influence on ABCC1 mediated drug resistance in cells or ABCG2 mediated drug resistance in S1 M1 80 cells. These show that crizotinib significantly sensitized ABCB1 overexpressing Erythropoietin cells to anticancer agents that are ABCB1 substrates. Crizotinib changed ABCB1 mediated MDR in nude mouse xenografts An existing KBv200 cell xenograft type in female nude mice was used to evaluate the efficacy of crizotinib to reverse the resistance to paclitaxel in vivo. There is no significant difference in tumor size between animals treated separately with saline, crizotinib or paclitaxel, suggesting the in vivo resistance to paclitaxel. But, the combination of paclitaxel and crizotinib created a substantial inhibition of tumour growth compared with animals treated with saline, paclitaxel, or crizotinib alone. The percentage of tumour growth inhibition by the combination was 46. One of the. Furthermore, in the doses tested, no mortality or apparent reduction in body weight was noticed in the combination treatment groups, indicating that the combination regime did not increase the incidence to Avagacestat 1146699-66-2 of toxic side effects. Crizotinib enhanced the accumulation of doxorubicin and rhodamine 123 in MDR cells overexpressing ABCB1 The above indicated that crizotinib could boost the sensitivity of MDR cancer cells to specific ABCB1 substrate anticancer drugs. To comprehend the underlying mechanisms, the intracellular accumulation of doxorubicin and rhodamine 123 within the presence or absence of crizotinib was evaluated by flow cytometric analysis. Upon incubation with the fluorescent substrates alone, intracellular fluorescence intensity of doxorubicin was notably higher in the KB and MCF 7 cells than that in the KBv200 and MCF 7/adr cells, while that of rhodamine 123 was 18. 3 fold higher in 12 and KB. 5 fold higher in MCF 7 cells, in contrast to KBv200 and MCF 7/adr cells respectively. If the KBv200 and MCF 7/adr cells were treated with crizotinib.