Angiogenesis is required for solid tumor growth and facilitates tumor progression and metastasis. The inhibition effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent, on expression of growth factors were investigated using human pulmonary adenocarcinoma cell line, A549. The A549 cells were divided into four groups: control group, 106 mg/ml gemcitabine treated group, 104 mg/ml TNP-470 treated group and gemcitabine+TNP-470 treated group. The mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors, FMS-like tyrosine kinase-1 (FLT-1) and kinase insert domain-containing receptor (KDR), in different groups were measured. The growth of A549 cell cultured with gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. Although gemcitabine (106 mg/ml) alone and TNP-470 (104 mg/ml) alone had no effect on the mRNA and protein expression of VEGF and its receptors (FLT-1, KDR) in A549 cells compared to the control (P>0.05), 106 mg/ml gemcitabine in combination with 104 mg/ml TNP-470 had significant effect (P<0.01). Moreover, combination of the two drugs significantly inhibited the mRNA expression of VEGF, FLT-1 and KDR compared to either drug alone (P<0.05). This study suggests that combined treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and antineoplastic effects in lung cancer cells in vitro. The inhibition effects of O- (chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent, on expression of growth factors were investigated using human pulmonary adenocarcinoma cell line, A549. The A549 cells were divided into four groups: control group, 106 mg / ml gemcitabine treated group, 104 mg / ml TNP-470 treated group and gemcitabine + The expression of vascular endothelial growth factor (VEGF) and its receptors, FMS-like tyrosine kinase-1 (FLT-1) and kinase insert domain-containing receptor Gemcitabine alone or TNP-470 (104 mg / ml) alone had no effect on the mRNA and protein expression of VEGF and its receptors (gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. FLT-1, KDR ) in A549 cells compared to the control (P> 0.05), 106 mg / ml gemcitabine in combination with 104 mg / ml TNP-470 had significant effect (P <0.01) of VEGF, FLT-1 and KDR compared to either drug alone (P <0.05). This study suggests that combined treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and antineoplastic effects in lung cancer cells in vitro.