Departments of Internal Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, 90 Chilam-dong, Jinju 660-702, Korea.
School of Veterinary, Research Institute of Life Science, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Korea.
Molecules. 2020 Nov 20;25(22):5445. doi: 10.3390/molecules25225445.
We previously demonstrated that anthocyanins from the fruits of (AIMs) induced the apoptosis of hepatocellular carcinoma cells. However, many researchers argued that the concentrations of AIMs were too high for in vivo experiments. Therefore, we performed in vitro at lower concentrations and in vivo experiments for the anti-cancer effects of AIMs. AIMs inhibited the cell proliferation of Hep3B cells in a dose-dependent manner with a maximum concentration of 100 µg/mL. AIMs also inhibited the invasion and migration at 100 µg/mL concentration with or without the presence of TNF-α. To establish the relevance between the in vitro and in vivo results, we validated their effects in a Xenograft model of Hep3B human hepatocellular carcinoma cells. In the in vivo test, AIMs inhibited the tumorigenicity of Hep3B cells in the xenograft mouse model without showing any clinical signs of toxicity or any changes in the body weight of mice. AIMs inhibited the activation NF-κB and suppressed the NF-κB-regulated proteins, intra-tumoral microvessel density (IMVD) and the Ki67 activity of Hep3B xenograft tumors in athymic nude mice. In conclusion, this study indicates that AIMs have anti-cancer effects (inhibition of proliferation, invasion, and angiogenesis) on human hepatocellular carcinoma xenograft through the inhibition of NF-κB and its target protein.
我们之前的研究表明，（AIMs）果实中的花色苷可诱导肝癌细胞凋亡。然而，许多研究人员认为，AIMs 的浓度对于体内实验来说太高了。因此，我们在较低浓度下进行体外实验，并进行体内实验以研究 AIMs 的抗癌作用。AIMs 以剂量依赖性方式抑制 Hep3B 细胞的增殖，最大浓度为 100µg/mL。AIMs 还可抑制在存在或不存在 TNF-α 的情况下，浓度为 100µg/mL 时的侵袭和迁移。为了确定体外和体内结果之间的相关性，我们在 Hep3B 人肝癌细胞的异种移植模型中验证了它们的作用。在体内试验中，AIMs 抑制了异种移植小鼠模型中 Hep3B 细胞的致瘤性，而没有表现出任何毒性的临床迹象或小鼠体重的任何变化。AIMs 抑制 NF-κB 的激活并抑制 NF-κB 调节的蛋白质、肿瘤内微血管密度 (IMVD) 和 Hep3B 异种移植肿瘤的 Ki67 活性。总之，这项研究表明，AIMs 通过抑制 NF-κB 及其靶蛋白，对人肝癌异种移植具有抗癌作用（抑制增殖、侵袭和血管生成）。
