title: Effect of new oxicam derivatives on efflux pumps overexpressed in resistant a human colorectal adenocarcinoma cell line.
abstract: BACKGROUND
  Oxicams are non-steroidal anti-inflammatory drugs (NSAIDs). Antitumor potential of NSAIDs has often been reported in literature. We studied antitumor activity of newly synthesized oxicam derivatives (PR17 and PR18) against doxorubicin-sensitive and resistant human colorectal adenocarcinoma cells (LoVo and LoVo/Dx).
  
  
  METHODS
  The cytotoxicity of oxicam derivatives alone and in combination with doxorubicin was assessed. Inhibition of P-glycoprotein (ABCB1) transport activity was monitored by flow cytometry. Expression of ABCB1 gene was analyzed by semi-quantitative reverse transcription PCR, while ABCB1 protein expression was assessed by western blotting.
  
  
  RESULTS
  Oxicam derivative PR18 was more cytotoxic to cancer cells than PR17. PR18 was observed to sensitize LoVo/Dx cells to doxorubicin and was identified as an effective multidrug resistance modulator. Additionally, ABCB1 expression was reduced in the presence of PR18.
  
  
  CONCLUSIONS
  PR18 was identified as an effective modulator in LoVo/Dx resistant human colorectal adenocarcinoma cells which overexpressed ABCB1 efflux pump.
authors.affiliation: Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland kamila.sroda-pomianek@umed.wroc.pl.
authors.forename: Kamila
authors.initials: K
authors.lastname: Środa-Pomianek
authors.affiliation: Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Wesołowska
authors.affiliation: Department of Chemistry of Drugs, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Berenika
authors.initials: B
authors.lastname: Szczęśniak-Sięga
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Puła
authors.affiliation: Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dzięgiel
authors.affiliation: Department of Chemistry of Drugs, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Maniewska
authors.affiliation: Department of Chemistry of Drugs, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Wiesław
authors.initials: W
authors.lastname: Malinka
authors.affiliation: Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Palko-Łabuz
authors.affiliation: Department of Biophysics, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Michalak
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003499:Cyclic S-Oxides / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D013843:Thiazines / Q000008:administration & dosage*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D003499:Cyclic S-Oxides; D013843:Thiazines; C000599968:oxicam PR18; D004317:Doxorubicin
keywords: Multidrug resistance (MDR); P-glycoprotein; cyclooxygenase 2 (COX2); non-steroidal anti-inflammatory drugs (NSAIDs)