title: [Reversal of multidrug resistance of tumor cells by FG020327 and its mechanism].
abstract: OBJECTIVE
  Over-expression of P-glyco-protein (P-gp) in tumor cells results in multidrug resistance (MDR), and failure of chemotherapy. Combined therapy of MDR-related cytotoxins plus MDR modulators is a promising strategy to overcome clinical MDR. This study was to explore MDR reversal activity of a novel compound FG020327, and its mechanism.
  
  
  METHODS
  MTT assay was used to evaluate MDR reversal activity of FG020327 in 2 P-gp expressing tumor cell lines, KBv200 and MCF-7/ADR. Adriamycin (ADM) accumulation in MCF-7/ADR cells was detected by fluorescence spectrophotometry. The effect of FG020327 on P-gp function was showed by rhodamine 123 (Rh123) accumulation and efflux in KBv200 cells.
  
  
  RESULTS
  FG020327 significantly enhanced sensitivity of MDR cells to anti- tumor drugs. Five mumol/L of FG020327 enhanced sensitivity of KBv200 cells to vincristine (VCR) by 44.9 folds, the reversal activity of which was 3 times that of verapamil (VRP). However, FG020327 had little effect on drug-sensitive MCF-7 cells and KB cells. FG020327 of 2.5, 5, and 10 mumol/L also enhanced ADM accumulation in MCF-7/ADR cells by 2.3, 2.7, and 3.7 folds, respectively, but didn't affect ADM accumulation in MCF-7 cells. FG020327 enhanced Rh123 accumulation in KBv200 cells,but not in KB cells.
  
  
  CONCLUSIONS
  FG020327 is an efficient modulator. The reversal of drug-resistance by FG020327 is probably related to enhanced anti-tumor drug accumulation, and inhibition of P-gp function in MDR tumor cells.
authors.affiliation: Research Department, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, 510060, P. R. China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Chen
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Su-Li
authors.initials: SL
authors.lastname: Yan
authors.forename: Yong-Ju
authors.initials: YJ
authors.lastname: Liang
authors.forename: Li-Wu
authors.initials: LW
authors.lastname: Fu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D012235:Rhodamines / Q000493:pharmacokinetics; D014750:Vincristine / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007093:Imidazoles; D012235:Rhodamines; D014750:Vincristine; D004317:Doxorubicin