title: Low dose chemotherapeutic drugs without overt cytotoxic effects decrease the secretion of VEGF by cultured human tumor cells: a tentative relationship between drug type and tumor cell type response.
abstract: BACKGROUND
  The metronomic use of chemotherapeutic drugs is presumed to have anti-angiogenic effect. In the current study, we aimed to test the effects of lower doses of cytotoxic agents on VEGF secretion from tumor cell lines.
  
  
  METHODS
  We tested the cytotoxic effects of widely used chemotherapeutic drugs including 5-florouracil, irinotecan, oxaliplatin, paclitaxel and docetaxel in tumor cell lines, MCF-7 (human breast cancer cell line) HT-29 (human colon cancer cell line) and a primary gastric cancer cell line and calculated the IC50 values. We've also assayed the effects of the lower doses of chemotherapeutic drugs on the levels of VEGF secreted by tumor cells in vitro.
  
  
  RESULTS
  The human primary gastric cancer cells were more resistant to 5-FU and oxaliplatin than the HT29 and MCF-7 cell lines (p < 0.001). No significant differences were noticed in terms of the IC50 values of the irinotecan, docetaxel and paclitaxel among the studied tumor cell lines (p > 0.05). The test drugs yielded significant decreases in VEGF levels at the doses of -2 log of IC50 values in MCF-7 and primary gastric cancer cell lines. While 5-florouracil did not inhibit the VEGF secretion of HT-29 cell line, irinotecan, oxaliplatin, docetaxel and paclitaxel significantly decreased the levels of secreted VEGF.
  
  
  CONCLUSIONS
  Our results suggest that lower doses of chemotherapeutic drugs decrease VEGF secretion from tumor cells without causing substantial cell killing. The data suggest the occurrence of a kind of selective drug-tumor cell type relationship.
authors.affiliation: Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Sedef Hande
authors.initials: SH
authors.lastname: Aktas
authors.forename: Hakan
authors.initials: H
authors.lastname: Akbulut
authors.forename: Nalan
authors.initials: N
authors.lastname: Akgun
authors.forename: Fikri
authors.initials: F
authors.lastname: Icli
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D000077146:Irinotecan; D061986:MCF-7 Cells; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D000077143:Docetaxel; D000077146:Irinotecan; D017239:Paclitaxel; D005472:Fluorouracil; D002166:Camptothecin