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  • Title: Paclitaxel nanosuspension coated with P-gp inhibitory surfactants: II. Ability to reverse the drug-resistance of H460 human lung cancer cells.
    Author: Gao L, Liu G, Ma J, Wang X, Wang F, Wang H, Sun J.
    Journal: Colloids Surf B Biointerfaces; 2014 May 01; 117():122-7. PubMed ID: 24632038.
    Abstract:
    PURPOSE: The present studies evaluated the ability of paclitaxel (PTX) nanosuspension coated with TPGS to reverse drug-resistance of P-glycoprotein (P-gp)-overexpressing H460 human lung cancer cells. METHOD: P-gp expression level of H460 cells was detected by western blot method. MTT assay was used to investigate in vitro cytotoxicity of PTX formulations and the resistance index (RI) of H460/RT cells. At last the antitumor efficacy of PTX nanosuspension was evaluated in resistant H460 cells xenograft Balb/c mice. RESULTS: The P-gp expression level of H460/RT cells was four times more than that of sensitive H460 cells. TPGS could reduce the P-gp expression by 25.41% at a concentration of 100 μg/ml after 24h exposure. Both PTX solution and nanosuspension exhibited obvious cytotoxicity against sensitive H460 cells. When H460/RT cells were treated, PTX nanosuspension showed significantly higher cytotoxicity compared with PTX solution, with much lower IC50 value and RI at each time point. After intravenous administration PTX nanosuspension exhibited about 5-fold increase in the inhibition rate of tumor growth compared with the mixed solution of PTX and TPGS. CONCLUSIONS: PTX nanosuspension coated with TPGS could effectively reverse drug resistance of H460/RT cells. The usage of TPGS as stabilizers on the surface of nanocrystals of insoluble anticancer drugs may be an effective approach to overcome the multi-drug resistances (MDR).
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