从抑制JAK2/STAT3/miR-21通路角度探讨蟾皮非极性组份蟾毒灵对肝癌放射增敏作用及其机制

Hepatocellular carcinoma is one of the most common malignant diseases in the world. Radiotherapy (RT) has been one of useful treatment of hepatocellular carcinoma. However, radiotherapeutic effects are still limited by hypoxia hepatocellular carcinoma cells with their high proliferative characteristic. To develop one novel radiosensitizer which can improve radiotherapeutic effects is necessary. Traditional Chinese medicine Toad skin and Huachansu, which have been widely used for liver cancer treatment, were demonstrated as effective radiosensitizer in many clinical trials. But the molecular mechamism remains unclear because of its complex compositions which need to be further researched and developed. Bufalin, one of non-polar fraction from toad skin, can improve the radiosensitivity of HCC cells by inhibiting the JAK2 /STAT3 signal transduction pathway and miR-21 in our previous study. Other previous study showed that the JAK2 /STAT3 signal transduction pathway can regulate and control the miR-21. Therefore, in this study we will further find the molecular mechamism of bufalin-mediated radiosensitization from the aspect of inhibiting JAK2/STAT3/miR-21 pathway which would lead to improvement in liver cancer by irradiation treatment in the future.

原发性肝癌是目前最常见的恶性肿瘤之一，放疗已成为治疗原发性肝癌的有效手段之一。然而由于肝癌细胞具有高增殖性导致肿瘤内部存在大量乏氧细胞，极大地限制了放疗的剂量和疗效，急需在肝癌的放疗中使用放疗增敏药物以提高放疗疗效。蟾皮水提物华蟾素在临床中被认为是一种有效的放疗增敏药物，然而其成分复杂有待于进一步研究和开发。蟾毒灵是蟾皮水提物中的非极性组份，我们前期研究发现蟾毒灵对肝癌细胞具有放疗增敏作用，并且初步研究发现其机制与抑制放疗后JAK2/STAT3细胞信号通路激活以及抑制miR-21表达有关。既往研究表明JAK2/STAT3通路能调控miR-21表达，结合前期研究结果，因此本研究将揭示肝癌放射性抵抗是否与JAK2/STAT3/miR-21通路有关，蟾毒灵放射增敏作用机制是否与抑制该通路有关，最终为明确蟾皮非极性组份蟾毒灵放疗增敏作用机制、寻找中药放射增敏剂提供依据。

原发性肝癌是目前最常见的恶性肿瘤之一，放疗已成为治疗原发性肝癌的有效手段之一。然而由于肝癌细胞具有高增殖性导致肿瘤内部存在大量乏氧细胞，极大地限制了放疗的剂量和疗效，急需在肝癌的放疗中使用放疗增敏药物以提高放疗疗效。蟾皮水提物华蟾素在临床中被认为是一种有效的放疗增敏药物，然而其成分复杂有待于进一步研究和开发。本实验研究证实了蟾毒灵-蟾皮水提物中的非极性组份，其对肝癌细胞具有放疗增敏作用；肝癌放射性抵抗与JAK2/STAT3/miR-21通路激活有关，蟾毒灵放射增敏作用机制与抑制该通路有关。通过临床数据统计表明，华蟾素能提高肝癌患者的放疗敏感性。