Drug resistance and P-glycoprotein expression in endothelial cells of newly formed capillaries induced by tumors

Anticancer Res. Jul-Aug 1998;18(4C):2977-80.

Abstract

The inhibitory effects of vincristine (VCR) with or without verapamil (VER) on angiogenesis in mouse subcutaneous fascia induced by mouse sarcoma 180 cells were assessed using the dorsal air sac method. VCR combined with VER had inhibitory effects on tumor-induced angiogenesis, but VCR alone did not inhibit capillarization. The chemosensitivity of human umbilical vein endothelial cells (HUVEC) and tumor-derived endothelial cells from rat KMT-17 fibrosarcoma (TEC) was examined using the microculture tetrazolium assay. VCR and taxol had strong anti-proliferative activity against HUVEC, but only weakly inhibited the proliferation of TEC. In combination with VER, VCR and Taxol inhibited the proliferation of TEC. Cisplatin, mitomycin C, and 5-fluorouracil had weakly anti-proliferative activity against both HUVEC and TEC. Expression of P-glycoprotein (P-gp) was found in TEC, but not in HUVEC using western blot analysis. These findings indicate that drug resistance and P-gp expression appeared on newly formed capillaries induced by rodents tumors.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Blotting, Western
  • Calcium Channel Blockers / pharmacology
  • Cell Division / drug effects
  • Cells, Cultured
  • Drug Resistance, Neoplasm
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism*
  • Paclitaxel / administration & dosage
  • Paclitaxel / pharmacology
  • Rats
  • Sarcoma 180 / blood supply*
  • Sarcoma 180 / drug therapy
  • Sarcoma 180 / metabolism
  • Umbilical Veins / cytology
  • Verapamil / administration & dosage
  • Verapamil / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Calcium Channel Blockers
  • Verapamil
  • Paclitaxel