Kasuya Kazuhiko, Tsuchida Akihiko, Suzuki Minako, Nagakawa Yuichi, Tanaka Hiroaki, Ota Hiroshi, Itoi Takao, Aoki Tatsuya
Dedpartment of Surgery, Tokyo Medical University Hospital , Tokyo, Japan.
Hepatogastroenterology. 2012 Jan-Feb;59(113):272-5. doi: 10.5754/hge11377.
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.
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.
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.
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.
