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.

中文翻译：

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丹参酮I通过活性氧介导的内质网应激和抑制p53 / DRAM介导的人肝细胞自噬诱导细胞凋亡。

人肝细胞癌（HCC）是最常见的肝癌类型，并且死亡率很高。尽管进行了外科手术治疗，放疗和化疗，晚期肝癌患者的中位生存期仍然很低。有证据表明，丹参酮（TA）I对多种癌症均表现出抗增殖活性。但是，TA I在肝癌中的作用及其机制仍然未知。在这里，我们确定了TA I对HCC细胞株HepG2和Huh7的抗癌潜力。使用细胞计数试剂盒8测定法分析细胞活力。流式细胞仪用于分析细胞周期和凋亡。蛋白质印迹用于检测蛋白质表达和磷酸化水平。发现TA I抑制HepG2和Huh7细胞增殖，诱导G0 / G1期停滞并触发细胞凋亡。我们进一步探讨了TA I介导的细胞凋亡的分子机制。我们的结果表明，TA I通过下调细胞周期蛋白D1表达和上调p21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HepG2和Huh7细胞中的p53 /损伤调节自噬调节剂（DRAM）介导的自噬来诱导细胞凋亡。因此，TA I可能是治疗HCC的抗癌药物。TA I通过活性氧介导的内质网应激和抑制HepG2和Huh7细胞中的p53 /损伤调节自噬调节剂（DRAM）介导的自噬来诱导细胞凋亡。因此，TA I可能是治疗HCC的抗癌药物。TA I通过活性氧介导的内质网应激和抑制HepG2和Huh7细胞中的p53 /损伤调节自噬调节剂（DRAM）介导的自噬来诱导细胞凋亡。因此，TA I可能是治疗HCC的抗癌药物。