Single nucleotide polymorphism of multidrug-resistance 1 and anti- multidrug-resistance 1 single chain antibody treatment for the pancreatic cancer cell line

Hepatogastroenterology. 2012 Jan-Feb;59(113):272-5. doi: 10.5754/hge11377.

Abstract

Background/aims: 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.

Methodology: 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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antibodies, Neutralizing / pharmacology*
  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Fluorouracil / metabolism
  • Fluorouracil / pharmacology*
  • Humans
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Polymorphism, Single Nucleotide*
  • Single-Chain Antibodies / pharmacology*
  • Time Factors

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibodies, Neutralizing
  • Antimetabolites, Antineoplastic
  • Single-Chain Antibodies
  • Fluorouracil