Moxifloxacin increases anti-tumor and anti-angiogenic activity of irinotecan in human xenograft tumors

Debby Reuveni, Drora Halperin, Ina Fabian, Galia Tsarfaty, Nadir Askenasy, Itamar Shalit

Research output: Contribution to journalArticlepeer-review

Abstract

Camptothecins (CPTs) are topoisomerase I inhibitors chemotherapeutic agents used in combination chemotherapy. We showed previously that combination of moxifloxacin (MXF) and CPT induced inhibitory effects on topoisomerase I activity, on proliferation of HT-29 cells in vitro and enhanced apoptosis, compared to CPT alone. Analysis of secretion of the pro-angiogenic factors IL-8 and VEGF showed significant reduction by MXF. Using a murine model of human colon carcinoma xenograft, we compared the effects of MXF/CPT in vitro to MXF/irinotecan combination in vivo. We show that the MXF/CPT inhibitory effects observed in vitro are reflected in the inhibition of the progressive growth of HT-29 cells implanted in SCID mice. Using caliper measurements, Doppler ultrasonography, image analyses and immunohistochemistry of nuclear proteins (Ki-67) and vascular endothelial cells (CD-31) we show that addition of MXF (45 mg/kg) to a relatively ineffective dose of irinotecan (20 mg/kg), results in a 50% and 30% decrease, respectively, in tumor size and a decrease in Ki-67 staining. Power Doppler Ultrasound showed a significant, pronounced decrease in the number of blood vessels, as did CD-31 staining, indicating decreased blood flow in tumors in mice treated with MXF alone or MXF/irinotecan compared to irinotecan. These results suggest that the combination of MXF/irinotecan may result in enhanced anti-neoplastic/anti-angiogenic activity.

Original languageEnglish
Pages (from-to)1100-1107
Number of pages8
JournalBiochemical Pharmacology
Volume79
Issue number8
DOIs
StatePublished - Apr 2010

Keywords

  • Angiogenesis
  • Chemotherapy
  • Irinotecan
  • Moxifloxacin

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