Hepato-Pancreato-Biliary Surgery, Peking University Shenzhen Hospital, Guangdong, China.
Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):488-497. doi: 10.1080/21691401.2019.1709862.
Human hepatocellular carcinoma (HCC) is the most common type of liver cancer, and it has a high mortality rate. Despite surgical treatments, radiotherapy, and chemotherapy, the median survival of patients with advanced HCC is low. Evidence has shown that tanshinone (TA) I exhibits anti-proliferative activity against numerous cancers. However, the role of TA I and its mechanism in HCC remain unknown. Here, we determined the anti-cancer potential of TA I against HCC cell lines HepG2 and Huh7. Cell viability was analyzed using a Cell Counting Kit-8 assay. Flow cytometry was used to analyze cell cycles and apoptosis. Western blotting was used to detect protein expression and phosphorylation levels. TA I was found to inhibit cell proliferation, induce G0/G1 phase arrest, and trigger apoptosis in HepG2 and Huh7 cells. We further explored the molecular mechanism of TA I-mediated apoptosis. Our results showed that TA I induced G0/G1 phase arrest through downregulation of cyclin D1 expression and upregulation of p21 expression. TA I induced cell apoptosis via reactive oxygen species-mediated endoplasmic reticulum stress and by inhibiting p53/damage-regulated autophagy modulator (DRAM)-mediated autophagy in HepG2 and Huh7 cells. Therefore, TA I may be an anti-cancer drug candidate in the treatment of HCC.
人肝癌（HCC）是最常见的肝癌类型，其死亡率很高。尽管进行了手术治疗、放疗和化疗，晚期 HCC 患者的中位生存期仍然较低。有证据表明，丹参酮（TA）I 对多种癌症具有抗增殖活性。然而，TA I 在 HCC 中的作用及其机制尚不清楚。在这里，我们确定了 TA I 对 HepG2 和 Huh7 肝癌细胞系的抗癌潜力。使用细胞计数试剂盒-8 分析来分析细胞活力。通过流式细胞术分析细胞周期和细胞凋亡。通过 Western blot 检测蛋白表达和磷酸化水平。结果表明，TA I 抑制细胞增殖，诱导 HepG2 和 Huh7 细胞 G0/G1 期阻滞，并触发细胞凋亡。我们进一步探讨了 TA I 介导的细胞凋亡的分子机制。结果表明，TA I 通过下调 cyclin D1 的表达和上调 p21 的表达诱导 G0/G1 期阻滞。TA I 通过活性氧介导的内质网应激和抑制 p53/损伤调节自噬调节剂（DRAM）介导的自噬诱导 HepG2 和 Huh7 细胞凋亡。因此，TA I 可能是治疗 HCC 的一种抗癌药物候选物。
