Gemcitabine and paclitaxel suppress the production of vascular endothelial growth factor induced by deferoxamine in human non-small cell lung cancer A549 cells

Vascular endothelial growth factor (VEGF) plays an important role in the process of angiogenesis in many types of cancer, including non-small cell lung cancer (NSCLC), and angiogenesis inhibitors and standard chemotherapy exhibit synergy though an unknown mechanism. We therefore hypothesized that cytotoxic chemotherapy influences VEGF production and analyzed VEGF production in an NSCLCA549 cell line after treatment with standard chemotherapy. Paclitaxel inhibited the production of VEGF in A549 cells, while cisplatin and erlotinib did not. Paclitaxel and gemcitabine inhibited deferoxamine (DFX) (known to mimic hypoxia)-induced VEGF production in A549 cells. Erlotinib also inhibited DFX-induced VEGF production in A549 cells slightly, while cisplatin did not. We subsequently examined the effect of the interaction between paclitaxel or gemcitabine and VEGF protein. Paclitaxel and gemcitabine did not directly affect the binding of VEGF. Since VEGF is known as one of the HIF-1 target genes, we examined the effect of paclitaxel and gemcitabine on HIF-1α levels induced by DFXin A549 cells. Paclitaxel and gemcitabine inhibited DFX-induced HIF-1α in A549 cells. These findings may be useful for future treatment schedules, including anti-cancer agents in NSCLC.