DJ-927, a novel oral taxane, overcomes P-glycoprotein-mediated multidrug resistance in vitro and in vivo

Cancer Sci. 2003 May;94(5):459-66. doi: 10.1111/j.1349-7006.2003.tb01465.x.


DJ-927 is a novel taxane, which was selected for high solubility, non-neurotoxicity, oral bioavailability, and potent antitumor activity. In this study, we compared the in vitro and in vivo efficacy of DJ-927 with those of paclitaxel and docetaxel. DJ-927 exhibited stronger cytotoxicity than paclitaxel and docetaxel in various tumor cell lines, especially against P-glycoprotein (P-gp)-expressing cells. The cytotoxicity of DJ-927, unlike those of other taxanes, was not affected by the P-gp expression level in tumor cells, or by the co-presence of a P-gp modulator. When intracellular accumulation of the three compounds was compared, intracellular amounts of DJ-927 were much higher than those of paclitaxel or docetaxel, particularly in P-gp-positive cells. In vivo, DJ-927 showed potent antitumor effects against two human solid tumors in male BALB/c-nu/nu mice, and yielded significant life-prolongation in a murine liver metastasis model with male C57BL/6 mice, in which neither paclitaxel nor docetaxel was effective. The results demonstrate the superior efficacy of orally administered DJ-927 over intravenously administered paclitaxel or docetaxel against P-gp-expressing tumors, probably due to higher intracellular accumulation. A phase I clinical trials of DJ-927 is currently ongoing in the US.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Survival / drug effects
  • Colony-Forming Units Assay
  • Docetaxel
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Humans
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism
  • Paclitaxel / therapeutic use
  • Taxoids / therapeutic use
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / transplantation


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Paclitaxel
  • tesetaxel