Low-Dose Cadmium Upregulates VEGF Expression in Lung Adenocarcinoma Cells.
Cadmium (Cd) is a heavy metal and environmental toxin. Exposure to Cd has been associated with a variety of human cancers. In this study, we performed in vitro assays to examine the effects of cadmium chloride (CdCl₂) on A549 cells, a human lung adenocarcinoma cell line. Cd does not affect proliferation, migration, or apoptosis of A549 cells at concentrations of 0.1-10 μM. At 0.5 and 1 μM, Cd increases the expression of vascular endothelial growth factor (VEGF) (p < 0.05, p < 0.01, respectively), but not basic fibroblast growth factor (b-FGF) in A549 cells. The conditioned media were collected from the A549 cells treated with 1 μM Cd and were co-cultured with human umbilical vein endothelial cells (HUVECs). Upon treatment with the conditioned media, the proliferation and migration of HUVECs significantly increased (p < 0.01, p < 0.05, respectively), while apoptosis remained unchanged. In addition, 1 μM Cd increases the level of hypoxia inducible factor 1-α (HIF1-α), which is a positive regulator of VEGF expression. Although low-dose Cd does not directly affect the growth of lung adenocarcinoma cells, it might facilitate the development of tumors through its pro-angiogenic effects.
Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China. lfhmm2000@163.com.
Fuhong
F
Liu
Department of Geriatric Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China. wangbei1224@126.com.
Bei
B
Wang
Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China. liiqun99@163.com.
Liqun
L
Li
Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China. dong.fengyun@163.com.
Fengyun
F
Dong
Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China. chenxiaocui2015@sina.com.
Xiaocui
X
Chen
Children's Health Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China. liyanxj@sina.com.
Yan
Y
Li
School of Biomedical Engineering, Fourth Military Medical University, Changle West Road No. 169, Xi'an 710032, Shanxi, China. dongxiuzhen@fmmu.edu.cn.
Xiuzhen
X
Dong
The Research Center for Advanced Science and Technology, and Isotope Science Center, The University of Tokyo, 2-11-16, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. wada-y@lsbm.org.
Youichiro
Y
Wada
Department of Biology, Trent University, Peterborough, Ontario K9J 7B8, Canada. ckapron@trentu.ca.
Carolyn M
CM
Kapron
Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China. ju.liu@sdu.edu.cn.
Ju
J
Liu
D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D004785:Environmental Pollutants; D042461:Vascular Endothelial Growth Factor A; D002104:Cadmium; D016222:Fibroblast Growth Factor 2
VEGF; angiogenesis; cadmium; endothelial cell; lung adenocarcinoma