基于黄芩汤研发的中药复方PHY906诱导Cyclin D1降解治疗肝癌的机制研究

近年来，基于中医经方黄芩汤而开发的复方PHY906在肝癌等消化系统肿瘤领域的实验与临床研究，再次引起了人们对中医药抗肿瘤作用的关注。我们的前期研究显示复方PHY906含药血清可以在体外促进Cyclin D1的泛素化降解，抑制肝癌细胞生长。进一步的研究表明Cyclin D1的286位苏氨酸(T286)磷酸化可能是PHY906诱导的Cyclin D1泛素化降解的关键步骤之一。基于前期研究结果，本项目试图证实PHY906对小鼠肝癌组织内Cyclin D1的降解效应，并进一步探讨Cyclin D1的T286位点磷酸化是否为PHY906诱导的Cyclin D1降解的必要条件。此外，我们将阐明哪一种F-box蛋白参与了PHY906介导的Cyclin D1泛素化降解以及该蛋白在PHY906介导的肝癌抑制中的作用。通过以上研究为PHY906治疗肝癌的临床应用提供理论依据。

In recent years, the experimental and clinical research on PHY906, a herbal formula based on the classic Chinese medicines Huangqin decoction, has attracted people's attention on developing novel anti-cancer agent from Chinse Medicines. Our previous studies showed that the medicated serum of PHY906 can promote the ubiquitination-mediated protein degradation of cyclin D1 in vitro and inhibit the growth of hepatoma cells. Further studies have shown that phosphorylation of 286 threonine (T286) of cyclin D1 may be one of the key steps in PHY906 induced cyclin D1 ubiquitination. Based on the results of our previous studies in vitro, this project attempts to confirm the effect of PHY906 on cyclin D1 degradation in mice liver cancer, and further explore whether phosphorylation at T286 site of cyclin D1 is a necessary condition for the degradation of cyclin D1 induced by PHY906. In addition, we will clarify the specific F-box protein involved in the ubiquitination-mediated protein degradationof cyclin D1 induced by PHY906 and its role in PHY906-mediated liver cancer inhibition. Based on above studies, we will provide a theoretical basis for the clinical application of PHY906 in liver cancer treatment.