Zhang Li, Chai Zongtao, Kong Siyuan, Feng Jiling, Wu Man, Tan Jiaqi, Yuan Man, Chen Gan, Li Zhuo, Zhou Hua, Cheng Shuqun, Xu Hongxi
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Front Cell Dev Biol. 2021 Mar 12;9:644716. doi: 10.3389/fcell.2021.644716. eCollection 2021.
Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor prognosis. High expression level of cofilin 1 (CFL1) has been found in many types of cancers. However, the role of CFL1 in HCC hasn't been known clearly. Here, we found that CFL1 was up regulated in human HCC and significantly associated with both overall survival and disease-free survival in HCC patients. Nujiangexanthone A (NJXA), the caged xanthones, isolated from gamboge plants decreased the expression of CFL1, which also inhibited the migration, invasion and metastasis of HCC cells and Down regulation of CFL1 inhibited aggressiveness of HCC cells, which mimicked the effect of NJXA. Mechanism study indicated that, knockdown of CFL1 or treatment with NJXA increased the level of F-actin and disturbed the balance between F-actin and G-actin. In conclusion, our findings reveal the role of CFL1 in HCC metastasis through the CFL1/F-actin axis, and suggest that CFL1 may be a potential prognostic marker and a new therapeutic target. NJXA can effectively inhibit the metastasis of HCC cells by down regulating the expression of CFL1, which indicates the potential of NJXA for preventing metastasis in HCC.
肝细胞癌（HCC）是预后较差的恶性肿瘤之一。在多种癌症中均发现丝切蛋白1（CFL1）表达水平较高。然而，CFL1在HCC中的作用尚不清楚。在此，我们发现CFL1在人类HCC中上调，且与HCC患者的总生存期和无病生存期均显著相关。从藤黄植物中分离得到的笼形呫吨酮类化合物怒江呫吨酮A（NJXA）可降低CFL1的表达，这也抑制了HCC细胞的迁移、侵袭和转移，而CFL1的下调抑制了HCC细胞的侵袭性，其效果与NJXA类似。机制研究表明，敲低CFL1或用NJXA处理可增加F-肌动蛋白水平，并扰乱F-肌动蛋白与G-肌动蛋白之间的平衡。总之，我们的研究结果揭示了CFL1通过CFL1/F-肌动蛋白轴在HCC转移中的作用，并表明CFL1可能是一种潜在的预后标志物和新的治疗靶点。NJXA可通过下调CFL1的表达有效抑制HCC细胞的转移，这表明NJXA在预防HCC转移方面具有潜力。
