P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer

Surg Today. 1999;29(7):591-6. doi: 10.1007/BF02482982.

Abstract

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / pharmacology
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / physiopathology
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Humans
  • Mitomycins / pharmacology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / physiopathology
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Mitomycins
  • Doxorubicin