F-53B对人肝癌细胞HepG2和Hep3B的细胞毒性效应研究
Cytotoxic Effects of F-53B on Human Hepatoma Cells HepG2 and Hep3B
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摘要: 研究氯化多氟烷基醚磺酸（6：2 chlorinated polyfluorinated ether sulfonate，商品名F-53B）对人肝癌细胞HepG2和Hep3B的毒性效应，并初步探讨其作用机制。选择常用的全氟辛烷磺酸（perfluorooctane sulfonate，PFOS）和全氟辛酸（perfluorooctanoic acid，PFOA）与F-53B同时进行毒性评估，检测细胞形态、细胞活力、凋亡、活性氧（reactive oxygen species，ROS），过氧化氢酶（catalase，CAT）、超氧化物歧化酶（superoxide dismutase，SOD）、凋亡相关因子（Bax、Caspase-3、PARP、Caspase-9等）表达水平。F-53B对细胞活性具有明显的抑制作用且毒力显著大于PFOS，并呈剂量依赖性；F-53B显著诱导ROS释放和细胞凋亡，并降低了抗氧化酶CAT活性；进一步证明促凋亡相关因子（Bax、Caspase-3、PARP、Caspase-9）表达增加，抑制凋亡因子Bcl-2表达水平降低。F-53B可诱导细胞凋亡和氧化应激，且线粒体内在途径可能参与细胞毒性作用。Abstract: 6:2 chlorinated polyfluorinated ether sulfonate, known as F-53B, is widely used as an important substitute of perfluorooctane sulfonate (PFOS) in industry, which may bring serious environmental and health risks. In this study, we will explore the potential hepatotoxic effects and related mechanism induced by F-53B in human hepatoma cells. Three perfluorinated compounds, including F-53B, PFOS and perfluorooctanoic acid (PFOA), were selected to assess their effects on cell morphology, cell viability and apoptosis in HepG2 and Hep3B cells. Markers of oxidative stress, such as reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), were compared among these three compounds. The protein levels of several apoptosis-related factors were also detected after chemicals exposure. Treatment with F-53B resulted in strong dose-dependent decrease in hepatoma cell viability, the effect of which was significantly higher than those obtained in the group treated with PFOS or PFOA. F-53B induced ROS release and decreased the activity of antioxidant enzyme CAT. F-53B also caused cell apoptosis, which was proved by the increased expression of pro-apoptotic factors (Bax, Caspase-3, PARP, Caspase-9) and decreased expression level of apoptotic factor Bcl-2. F-53B can induce hepatoma cell apoptosis and oxidative stress through mitochondrial intrinsic pathway.
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Key words:
- F-53B /
- hepatocytes /
- apoptosis /
- oxidative stress
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