Clinical features of aflatoxin B1-exposed patients with liver cancer and the molecular mechanism of aflatoxin B1 on liver cancer cells

被引:33
作者
Zhou, Rui [1 ]
Liu, Meizhen [2 ]
Liang, Xiaoliu [2 ]
Su, Min [3 ]
Li, Rong [3 ]
机构
[1] Guangxi Med Univ, Affiliated Hosp 8, Guigang City Peoples Hosp, Dept Hepatobiliary Surg, Guigang 537100, Guangxi, Peoples R China
[2] Guangxi Med Univ, Coll Pharm, Nanning 530021, Peoples R China
[3] Guilin Med Univ, Key Lab Tumour Immunol & Microenvironm Regulat, 109 Huan Cheng North 2nd Rd, Guangxi 541004, Guilin, Peoples R China
基金
中国国家自然科学基金;
关键词
Aflatoxin B1; AKR7A; Cytotoxicity; Liver cancer; HEPATOCELLULAR-CARCINOMA; EXPRESSION; EXPOSURE; GUANGXI;
D O I
10.1016/j.etap.2019.103225
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Aflatoxin B1 (AFB1) induces hepatocellular carcinoma (HCC) through consumption of contaminated food in Southern China. Aldo-keto reductase-7A (AKR7A) functionally plays a potent role in the biodetoxification in the liver. In addition, hepatocellular lipid disorder has found to be closely linked to the development of HCC. This study was, therefore, designed to investigate the potent bioeffect of AKR7A on the lipid metabolism in AFB1-exposed hepatocellular carcinoma cells through assaying human cancerous samples and cell culture. In the baseline data, the HCC patients showed increased contents of AFB1 in sera and cancerous samples. In the clinical parameters, the HCC patients demonstrated changed lipid settings in sera. As revealed by immunostaining and immunoblotting, AFB1-elevated HCC sections showed marked down-regulation of AKR7A expression, accompanied with reduced ApoB expression and increased CD36, S6K1 expressions in the HCC. Studies in the human hepatocarcinoma line HepG2 also showed AFB1-exposure to increase ApoA1, LDL, TC, and TG contents; induce cell proliferation; and reduce hepatocellular AKR7A expression. Furthermore, AKR7A bioactivity was inactivated after treatment with perfluorooctane sulfonate (PFOS), an ApoB activator, in AFB1-dosed HepG2 cells. Collectively, our current findings suggest that hepatocellular AKR7A has a protective role against AFB1-induced cytotoxicity through the regulation of CD36, S6K1 and ApoB expression through the reduction of lipid utilization in malignant liver cells.
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页数:7
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