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Low-Dose Cadmium Upregulates VEGF Expression in Lung Adenocarcinoma Cells

1
Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China
2
Department of Geriatric Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China
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Children’s Health Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan 250014, Shandong, China
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School of Biomedical Engineering, Fourth Military Medical University, Changle West Road No. 169, Xi’an 710032, Shanxi, China
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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
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Department of Biology, Trent University, Peterborough, Ontario K9J 7B8, Canada
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the work.
Academic Editor: Paul B. Tchounwou
Int. J. Environ. Res. Public Health 2015, 12(9), 10508-10521; https://doi.org/10.3390/ijerph120910508
Received: 19 July 2015 / Revised: 13 August 2015 / Accepted: 25 August 2015 / Published: 28 August 2015
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. View Full-Text
Keywords: cadmium; VEGF; lung adenocarcinoma; endothelial cell; angiogenesis cadmium; VEGF; lung adenocarcinoma; endothelial cell; angiogenesis
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Liu, F.; Wang, B.; Li, L.; Dong, F.; Chen, X.; Li, Y.; Dong, X.; Wada, Y.; Kapron, C.M.; Liu, J. Low-Dose Cadmium Upregulates VEGF Expression in Lung Adenocarcinoma Cells. Int. J. Environ. Res. Public Health 2015, 12, 10508-10521.

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