β-lactoglobulin is important fraction in bovine milk. Selenium is an essential nutrient element. The apoptosis and autophagy induction of Se-β-Lg combined selenic acid in β-lactoglobulin on Hep G2 and Hep 3B cells were investigated in this study. MTT assay showed Se-β-Lg inhibited cells viability. Annexin V-FITC/PI and PI staining indicated Se-β-Lg triggered cells apoptosis and cell cycle arrest. Western blot of caspase-cascade suggested Hep G2 and Hep 3B cells occurred irreversible extrinsic apoptosis. TEM and protein expression of LC3 indicated Se-β-Lg induced cells autophagy. Further explore found Se-β-Lg induced up-regulation of p53 and Fas/FasL in Hep G2 cells. Simultaneously, N-acetyl-L-cysteine, pifithrin-α, Z-VAD-FMK and 3-MA were used. These results further demonstrated Se-β-Lg triggered autophagy and receptor-related apoptosis via p53-mediated Fas/FasL pathway in Hep G2 cells and induced autophagy and p53/Fas-independent caspase activation in Hep 3B cells. Our research revealed that Se-β-Lg had potential to act as chemopreventive compounds in HCC therapy.

β-乳球蛋白是牛乳中的重要组成部分。硒是必不可少的营养元素。研究了β-乳球蛋白中Se-β-Lg联合硒酸对Hep G2和Hep 3B细胞的凋亡和自噬诱导作用。MTT分析显示Se-β-Lg抑制细胞活力。Annexin V-FITC / PI和PI染色表明Se-β-Lg触发了细胞凋亡和细胞周期停滞。半胱天冬酶级联的蛋白质印迹表明Hep G2和Hep 3B细胞发生不可逆的外源性凋亡。LC3的TEM和蛋白质表达表明Se-β-Lg诱导的细胞自噬。进一步的研究发现，Se-β-Lg诱导了Hep G2细胞中p53和Fas / FasL的上调。同时，使用了N-乙酰基-L-半胱氨酸，菲菲-α，Z-VAD-FMK和3-MA。这些结果进一步证明，Se-β-Lg在Hep G2细胞中通过p53介导的Fas / FasL途径触发自噬和受体相关的凋亡，并在Hep 3B细胞中诱导自噬和不依赖p53 / Fas的caspase活化。我们的研究表明，Se-β-Lg在HCC治疗中具有作为化学预防化合物的潜力。