Effect of rapamycin-induced tumor vessel thrombosis combined with docetaxel in non-small-cell lung cancer

Anticancer Drugs. 2013 Apr;24(4):406-14. doi: 10.1097/CAD.0b013e32835ec3b0.

Abstract

Lung cancer remains incurable in many cases despite current chemotherapies. We explored an approach combining a recently described antiangiogenic drug, rapamycin, with standard docetaxel cytotoxic therapy on the growth of non-small-cell lung cancer. Rapamycin alone inhibited tumor growth and upregulated apoptosis, with more pronounced effects when rapamycin and docetaxel were combined. Tumor vessel endothelium damage and thrombosis was evident with rapamycin treatment; this was concomitant with decreased microvessel density. In contrast, docetaxel was not antiangiogenic and did not reduce proliferation in tumors, despite its known cytotoxicity. Our data represent a new promising therapeutic regimen against non-small-cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary*
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / transplantation
  • Docetaxel
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Ki-67 Antigen / analysis
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary*
  • Male
  • Mice
  • Mice, Nude
  • Microvessels / chemistry
  • Microvessels / drug effects
  • Microvessels / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Sirolimus / administration & dosage
  • Sirolimus / pharmacology
  • Specific Pathogen-Free Organisms
  • Taxoids / administration & dosage
  • Thrombosis / chemically induced*
  • Tumor Burden
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Ki-67 Antigen
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Taxoids
  • Docetaxel
  • Sirolimus