Inhibition of expression of vascular endothelial growth factor and its receptors in pulmonary adenocarcinoma cell by TNP-470 in combination with gemcitabine.
- Author:
Xue-fen WANG
1
;
Ling-fang TU
;
Li-hong WANG
;
Jian-ying ZHOU
Author Information
1. Department of Respirology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. wxfzy636@hotmail.com
- Publication Type:Journal Article
- MeSH:
Adenocarcinoma;
drug therapy;
Antineoplastic Combined Chemotherapy Protocols;
therapeutic use;
Cell Line, Tumor;
Cell Proliferation;
Cyclohexanes;
administration & dosage;
Deoxycytidine;
administration & dosage;
analogs & derivatives;
Disease Progression;
Gene Expression Regulation, Neoplastic;
Humans;
Lung Neoplasms;
drug therapy;
Neoplasm Metastasis;
Protein Structure, Tertiary;
Sesquiterpenes;
administration & dosage;
Vascular Endothelial Growth Factor A;
biosynthesis;
Vascular Endothelial Growth Factor Receptor-1;
biosynthesis;
Vascular Endothelial Growth Factor Receptor-2;
biosynthesis
- From:
Journal of Zhejiang University. Science. B
2006;7(10):837-843
- CountryChina
- Language:English
-
Abstract:
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.
