Inhibition of expression of vascular endothelial growth factor and its receptors in pulmonary adenocarcinoma cell by TNP-470 in combination with gemcitabine.
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, 10(-6) mg/ml gemcitabine treated group, 10(-4) 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 (10(-6) mg/ml) alone and TNP-470 (10(-4) 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), 10(-6) mg/ml gemcitabine in combination with 10(-4) 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.
Wang
Xue-fen
XF
Department of Respirology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. wxfzy636@hotmail.com
Tu
Ling-fang
LF
Wang
Li-hong
LH
Zhou
Jian-ying
JY
D000230:Adenocarcinoma / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003510:Cyclohexanes / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D017434:Protein Structure, Tertiary; D012717:Sesquiterpenes / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*; D000093542:Gemcitabine
D003510:Cyclohexanes; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D000093542:Gemcitabine