title: R-dl-verapamil downmodulates multidrug resistance of KBv200 cells to vincristine and doxorubicin.
abstract: OBJECTIVE
  To study the attenuation of multidrug resistance (MDR) by R-dl-verapamil (R-Ver) and the acute animal toxicity of R-Ver, and to compare these results of R-Ver with the results of dl-verapamil (Ver).
  
  
  METHODS
  Cytotoxicity was determined by tetrazolium (MTT) assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry. Acute animal toxicity was tested by i.p. drug administration in BALB/c mice.
  
  
  RESULTS
  R-Ver attenuated MDR of KBv200 cells to vincristine (VCR) and Dox. This attenuation ability was dose-related, and was also dependent on drug exposure time. R-Ver 1.25 mumol.L-1 increased the sensitivity of KBv200 cells to VCR (P < 0.01) with a 24-h period of drug exposure. R-Ver downmodulated MDR and increased cellular Dox accumulation of KBv200 cells as effectively as Ver, but possessed lower acute toxicity in BALB/c mice. While LD50 of Ver was 60 (49-73) mg.kg-1, LD50 of R-Ver was 166 (137-202) mg.kg-1.
  
  
  CONCLUSIONS
  R-Ver downmodulated the MDR to VCR and Dox at 1.25 mumol.L-1, and this effect on VCR can be realized with drug exposure duration of 24 h.
authors.affiliation: Nanjing University School of Medicine, China. yingfeng@nju.edu.cn
authors.forename: G
authors.initials: G
authors.lastname: Fang
authors.forename: Y L
authors.initials: YL
authors.lastname: Yang
authors.forename: J S
authors.initials: JS
authors.lastname: Li
authors.forename: Z X
authors.initials: ZX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D006801:Humans; D007624:KB Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D013237:Stereoisomerism; D014700:Verapamil / Q000494:pharmacology* / Q000633:toxicity; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D004317:Doxorubicin; D014700:Verapamil