In vivo anti-tumor effect of PEG liposomal doxorubicin (DOX) in DOX-resistant tumor-bearing mice: Involvement of cytotoxic effect on vascular endothelial cells

Ken ichi Ogawara, Keita Un, Ken ichi Tanaka, Kazutaka Higaki, Toshikiro Kimura

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68 Citations (Scopus)

Abstract

We evaluated the in vivo anti-tumor effect of polyethylene glycol-modified liposomal doxorubicin (PEG liposomal DOX) in the DOX-resistant Colon-26 cancer cells (C26/DOX)-bearing mice model. IC50 value of DOX to C26/DOX in vitro (40.0 μM) was about 250 times higher than that to control C26 (C26/control) (0.15 μM). However, in vivo anti-tumor effect of PEG liposomal DOX was similar in both C26/control- and C26/DOX-bearing mice, suggesting that the in vivo anti-tumor effect of PEG liposomal DOX was not directly reflecting the sensitivity of these tumor cells to DOX. IC50 value (0.10 μM) of DOX to HUVEC, a model vascular endothelial cell, was similar to that of C26/control. Double immunohistochemical staining of vascular endothelial cells and apoptotic cells within the tumor tissue after intravenous administration of PEG liposomal DOX showed that the extent of co-localization of apoptotic cells with endothelial cells was significantly higher for C26/DOX tumors (60%) than C26/control ones (20%), suggesting that the apoptosis is caused preferentially for vascular endothelial cells in C26/DOX tumor. From these results, it was suggested that the cytotoxic effect of DOX on vascular endothelial cells in the tumor would be involved in the in vivo anti-tumor effect of PEG liposomal DOX in C26/DOX-bearing mice.

Original languageEnglish
Pages (from-to)4-10
Number of pages7
JournalJournal of Controlled Release
Volume133
Issue number1
DOIs
Publication statusPublished - Jan 5 2009

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Keywords

  • Apoptosis
  • Doxorubicin
  • Liposome
  • P-glycoprotein
  • Vascular endothelial cells

ASJC Scopus subject areas

  • Pharmaceutical Science

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