School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Cancer Biol Ther. 2023 Dec 31;24(1):2229958. doi: 10.1080/15384047.2023.2229958.
Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with increasing incidence rates and high mortality rates. The currently available methods for treating HCC include surgery, radiotherapy or chemotherapy, but all of them have limitations. Therefore, developing novel therapeutic methods for HCC is in great need. Here, in this study, we found that tanshinone I, a small molecule compound, inhibited the proliferation of HCC cells in a dose-dependent manner. We also observed that Tanshinone I destabilized genomes by inhibiting both NHEJ and HR repair pathways, which are responsible for repairing DNA double strand breaks (DSBs). Mechanistically, this compound suppressed the expression of 53BP1, and the recruitment of RPA2 to DNA damage sites. Importantly, we demonstrated that combining Tanshinone I with radiotherapy exhibited better therapeutic potential for treating HCC.
肝细胞癌（HCC）是最常见的恶性肿瘤之一，其发病率和死亡率呈上升趋势。目前治疗 HCC 的方法包括手术、放疗或化疗，但这些方法都有其局限性。因此，非常需要开发治疗 HCC 的新方法。在这项研究中，我们发现丹参酮 I 是一种小分子化合物，能以剂量依赖的方式抑制 HCC 细胞的增殖。我们还观察到丹参酮 I 通过抑制非同源末端连接（NHEJ）和同源重组（HR）修复途径来破坏基因组，这两种途径负责修复 DNA 双链断裂（DSBs）。在机制上，这种化合物抑制了 53BP1 的表达，以及 RPA2 向 DNA 损伤部位的募集。重要的是，我们证明了丹参酮 I 与放疗联合使用具有更好的治疗 HCC 的潜力。
