title: Single nucleotide polymorphism of multidrug-resistance 1 and anti- multidrug-resistance 1 single chain antibody treatment for the pancreatic cancer cell line.
abstract: OBJECTIVE
  Anticancer drugs are essential to pancreatic cancer therapy. The multidrug-resistance 1 (MDR1) gene codes for one of the ATP binding cassette (ABC) transporters. The neutralizing antibody of MDR1 reduces the activity of MDR1 and may add to the sensitivity of anti-cancer drugs. We investigated the relationship of the single nucleotide polymorphisms (SNPs), 2677G and 3435C, in the MDR1 gene and the effect of the anti-MDR1 single chain antibody (scAb) using pancreatic cancer cell lines.
  
  
  METHODS
  We exposed the pancreatic cancer cell lines, AsCP-1, Panc-1, BxPC-3, MIAPaCa-2 and QGP-1 to 0.1-1,000µ g/mL of 5-FU for 72h and calculated the cytotoxic reactions. Combined therapy with an established anti-MDR1 neutralizing scAb and 10µg/mL of 5-FU was also performed.
  
  
  RESULTS
  AsCP-1 contained wild types of MDR1 2677G and 3435C, and showed the most 5-FU resistance. The anticancer effect of AsPC-1 increased with anti-MDR1 scAb, but the effect was not significant compared with other cell lines.
  
  
  CONCLUSIONS
  The cells with the wild type SNPs of MDR1 showed drug resistance, but we were not able to confirm a remarkable effect of the anti-MDR1 antibody.
authors.affiliation: Dedpartment of Surgery, Tokyo Medical University Hospital , Tokyo, Japan. kasuya-k@jcom.home.ne.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kasuya
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuchida
authors.forename: Minako
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nagakawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ota
authors.forename: Takao
authors.initials: T
authors.lastname: Itoi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Aoki
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D057127:Single-Chain Antibodies / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D057134:Antibodies, Neutralizing; D000964:Antimetabolites, Antineoplastic; D057127:Single-Chain Antibodies; D005472:Fluorouracil