title: Paclitaxel nanosuspension coated with P-gp inhibitory surfactants: II. Ability to reverse the drug-resistance of H460 human lung cancer cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China. Electronic address: leiglswj@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China. Electronic address: liuguiy@gmail.com.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing 100048, China. Electronic address: sjunzh07@163.com.
authors.forename: Junzhong
authors.initials: J
authors.lastname: Sun
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D013501:Surface-Active Agents / Q000494:pharmacology*; D013535:Suspensions; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013501:Surface-Active Agents; D013535:Suspensions; D017239:Paclitaxel
keywords: H460 human lung cancer cells; Multi-drug resistance; Nanosuspension; P-gp; Paclitaxel