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The aim of this study was to investigate the antitumor effect of docetaxel (DTX) loaded Pluronic P105/F127 mixed micelles (PF-DTX) against drug-resistant Lung Adenocarcinoma Cell Line A549/Taxol.DTX loaded Pluronic P105/F127 mixed micelles was prepared by thin-film hydration method and optimized using central composite design.Modulation of multidrug resistance (MDR) by Pluronic mixed micelles was evaluated in Taxol-resistant Human lung adenocarcinoma cell line A549 (A549/Taxol).In vitro cytotoxicity was determined by CCK8 assay,while cellular apoptosis was detected by cell nuclei staining and Annexin V-FITC apoptosis detection kit.Cell cycle arrest was also confirmed by flow cytometry.Additionally,in vivo antitumor efficacy of PF-DTX was extensively evaluated in comparison with Taxotere.The in vitro release of DTX from the mixed micelles presented a sustained-release property.The in vitro cytotoxicity assay showed that on the sensitive A549 cells,the IC50 values for Taxotere and PF-DTX were similar,while on A549/Taxol cells,IC50 values ofPF-DTX (0.059μg/ml) was much lower than those of Taxotere injection (0.593μg/ml) and the flee DTX (0.857μtg/ml),which showed superior hypersensitizing effect on MDR cells.The enhanced anti-cancer efficacy of PF-DTX in vitro was associated with DTX-induced apoptosis and cell arrest in the G2/M phase.In BALB/c mice bearing A549/Taxol tumor xenografts,stronger antitumor efficacy was shown in PF-DTX group,with good correlation between in vitro and in vivo.Therefore,it was concluded that Docetaxel loaded Pluronic P105/F127 mixed micelles significantly enhanced the anti-cancer activity of DTX and might be considered a promising drug delivery system to overcome MDR in lung cancer.