新抗癌天然产物SSPH在TAE术后缺氧环境下调控铁死亡抑制肝癌细胞增殖

肝癌是一种高致死率的恶性肿瘤，肝动脉栓塞术（TAE）是常用的治疗方式。铁死亡由铁依赖的氧化损伤引发，TAE后引起肿瘤局部缺氧，铁死亡诱导剂如索拉非尼可增加其治疗作用，但其调控机制尚未明确。本课题组由广西特色中药裂果薯中分离的皂苷单体SSPH具有良好的抗肝癌作用，我们的研究发现：SSPH通过ROS-Erk信号通路抑制肿瘤细胞增殖，且铁死亡抑制剂可阻断SSPH对肝癌细胞的抑制作用。我们认为SSPH极有可能通过ERK-HIF-铁死亡的信号通路抑制肝癌细胞增殖并增加TAE的治疗作用。在此，我们将对比常氧/缺氧下SSPH对人肝癌细胞株的铁死亡诱导作用与机制，以人肝癌裸鼠移植瘤模型验证其体内抑瘤作用；并以TAE/假手术±SSPH治疗大鼠肝原位鼠肝癌移植瘤模型，体内外结合验证SSPH在TAE术后缺氧环境下调控铁死亡的机制与TAE治疗增效作用，为具有铁死亡诱导作用的中药组分在TAE中的应用提供理论依据。

Hepatocellular carcinoma (HCC) is one of the most common causes of solid cancer mortality, transtherter arterial embolization (TAE) is commonly used in HCC treatment. Ferroptosis induced by iron depending oxidative damage, TAE combined ferroptosis inducer such as Sorafenib is effective. In post TAE HCC tissue, the mechanism between ferroptosis and hypoxia remains unclear. SSPH is a saponin separated from traditional anticancer Chinese medicine Schizocapsa plantaginea Hance by our group, we found that SSPH's is a ROS-Erk regulator and it’s anti-proliferation effect could be blocked by ferroptosis inhibitor. We believe that SSPH is most probably to inhibit HCC cell proliferation by ERK-HIF-ferroptosis pathway and improve the therapeutic effect of TAE. Here, we will analysis the effect and mechanism of SSPH by HCC cell model under normoxia and hypoxia. Further therapeutic effect of SSPH will verified in nude mice xenograft model. The mechanism of SSHP inducing ferroptosis under normoxia and hypoxia will verified in rat orthotopic hepatoma model with TAE. Our data will provide an important basis for the development of SSPH and other natural in TAE treatment.