The retinoid X receptor-selective ligand, LGD1069, inhibits tumor-induced angiogenesis via suppression of VEGF in human non-small cell lung cancer.
The present study determined the influence of a retinoid X receptor agonist LGD1069 on angiogenesis in non-small cell lung cancer. In A549 xenograft models, treatment with LGD1069 inhibited the growth and CD31 expression compared with control. In vivo angiogenesis assay utilizing hollow fiber, LGD1069 reduced density of capillary network induced by tumor cells. To determine the basis of these observations, we examined the expression of VEGF and activation of JNK and ERK in A549 cells exposed to LGD1069. Our data showed that LGD1069 decrease the VEGF expression of tumor cells in a dose-dependent manner. Furthermore, it was demonstrated that the decreasing expression of VEGF was consist with inhibition of JNK and ERK activation induced by LGD1069. Collectively, our results suggest a role of LGD1069 in treatment for non-small cell lung cancer by inhibition of tumor-induced angiogenesis.
Fu
Jianjiang
J
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Ding
Yan
Y
Huang
Dan
D
Li
Hongyan
H
Chen
Xiaoguang
X
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077610:Bexarotene; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000819:agonists* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D016588:Anticarcinogenic Agents; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D042461:Vascular Endothelial Growth Factor A; D000077610:Bexarotene; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3