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
Affiliations: Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey
Correspondence:
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Corresponding author: Dr. Hakan Akbulut, Department of Medical Oncology, Ankara University School of Medicine, Ankara 06100, Turkey. Tel.: +90 312 595 7712; Fax: +90 312 319 2283; E-mail: [email protected].
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.
Keywords: 5-florouracil, irinotecan, oxaliplatin, paclitaxel, docetaxel, VEGF, IC50, gastric cancer
