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Low dose chemotherapeutic drugs without overt cytotoxic effects decrease the secretion of VEGF by cultured human

Sedef Hande Aktas1, Hakan Akbulut, Nalan Akgun

  • 1Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey.

Cancer Biomarkers : Section a of Disease Markers
|March 14, 2013
PubMed
Abstract

Insights

Lower doses of chemotherapy drugs can reduce vascular endothelial growth factor (VEGF) secretion from tumor cells, suggesting a targeted anti-angiogenic effect without significant cell death. This highlights a selective drug-tumor cell relationship.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Metronomic chemotherapy is theorized to possess anti-angiogenic properties.
  • Investigating the impact of reduced cytotoxic agent concentrations on VEGF secretion is crucial for understanding novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the anti-angiogenic effects of sub-lethal doses of common chemotherapeutic agents.
  • To determine the impact of these agents on vascular endothelial growth factor (VEGF) secretion in various cancer cell lines.

Main Methods:

  • Cytotoxic effects and IC50 values of 5-fluorouracil, irinotecan, oxaliplatin, paclitaxel, and docetaxel were assessed in MCF-7, HT-29, and primary gastric cancer cell lines.
  • VEGF secretion levels were measured in vitro after treatment with lower doses of these chemotherapeutic drugs.

Main Results:

  • Primary gastric cancer cells exhibited higher resistance to 5-fluorouracil and oxaliplatin compared to MCF-7 and HT-29 cells.
  • Irinotecan, docetaxel, and paclitaxel showed similar IC50 values across all tested cell lines.
  • Lower doses (-2 log IC50) of tested drugs significantly reduced VEGF secretion in MCF-7 and primary gastric cancer cells, with 5-fluorouracil ineffective against HT-29 VEGF secretion.

Conclusions:

  • Sub-lethal concentrations of chemotherapeutic drugs can inhibit VEGF secretion from tumor cells, indicating a potential anti-angiogenic mechanism.
  • The findings suggest a selective interaction between specific drug-tumor cell types, offering a basis for tailored cancer therapies.
  • This approach may reduce systemic toxicity associated with conventional chemotherapy.

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