Zhen Ni, Jin Lei, Ma Ji, Zhu Jiabei, Gu Song, Wang Jing, Pan Qiuhui, Ni Xiaorong, Xu Min
Department of Laboratory Medicine, Shanghai Children’s Medical Center, School of medicine, Shanghai Jiaotong University.
Department of Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University.
Anticancer Drugs. 2018 Sep;29(8):756-766. doi: 10.1097/CAD.0000000000000646.
The ginsenoside Rg1, the primary pharmacologically active ingredient of the traditional Chinese herb ginseng, is widely used in the clinical treatment of diseases of the immune and nervous systems. Recent studies have shown that it also has an antitumor effect. In this study, we explored the effects of Rg1 on hepatoblastoma (HB) and its underlying mechanisms. We demonstrated that Rg1 significantly inhibited HB cell growth both in vivo and in vitro. Mechanistic studies revealed that Rg1 impaired homologous recombination and triggered double-strand breaks in HB cells by directly targeting CtBP-interacting protein (CtIP), a key double-strand break repair factor, which is highly expressed in HB tissues. Moreover, we also demonstrated that Rg1 sensitized HB cells to DNA-damaging agents both in vitro and in vivo. In conclusion, our data not only demonstrate the potential clinical application of Rg1 as a novel chemotherapeutic candidate but also offer a mechanism-based therapeutic option by which DNA-damaging agents can be used in combination with Rg1 to target HB.
人参皂苷Rg1是传统中药人参的主要药理活性成分，广泛应用于免疫和神经系统疾病的临床治疗。最近的研究表明，它还具有抗肿瘤作用。在本研究中，我们探讨了Rg1对肝母细胞瘤（HB）的影响及其潜在机制。我们证明，Rg1在体内和体外均能显著抑制HB细胞生长。机制研究表明，Rg1通过直接靶向CtBP相互作用蛋白（CtIP）损害同源重组并引发HB细胞中的双链断裂，CtIP是一种关键的双链断裂修复因子，在HB组织中高度表达。此外，我们还证明，Rg1在体内和体外均使HB细胞对DNA损伤剂敏感。总之，我们的数据不仅证明了Rg1作为新型化疗候选药物的潜在临床应用，还提供了一种基于机制的治疗选择，即DNA损伤剂可与Rg1联合用于靶向HB。
