期刊
MOLECULAR CANCER
卷 14, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12943-014-0274-0
关键词
Alcohol; Angiogenesis; Human hepatocellular cancer; Metastasis; Reactive oxygen species
资金
- Project of the National Natural Sciences Foundation of China
- Natural Science Foundation of Anhui Province
- NIH
- [81272258]
- [1308085MH121]
- [AA015407]
- [AA017226]
Background: Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC. Methods and results: We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-kappa B was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-kappa B signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-kappa B signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis. Conclusion: This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-kappa B-dependent VEGF and MCP-1 up-regulation.
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