肝癌是严重影响人类健康的疾病，居世界肿瘤相关死因的第三位。手术切除是目前肝癌治疗的首选方法，但是肝癌术后的5年复发率高达75％以上，严重制约了手术的疗效。因此，探寻能有效预防和抑制肝癌术后复发的方法是提高肝癌治疗质量的关键。
索拉菲尼（Sorafenib）是第一个用于治疗晚期肝癌的口服药物。通过抑制细胞内多种丝/苏氨酸激酶和酪氨酸激酶（如B-Raf和VEGFR等）的活性，索拉菲尼能抑制肿瘤细胞生长和血管生成。但是，尚不清楚索拉菲尼能否在通过手术治疗的早期肝癌抑制术后复发和转移。
1月27日，知名肝脏病研究期刊 Hepatology在线发表了上海生科院营养所谢东研究组与第二军医大学合作的关于索拉菲尼在早期肝癌治疗中的作用的最新研究结果。利用荧光素酶标记的异种原位移植（Orthotopic Xenograft）肝癌小鼠模型，冯宇雄、王涛和邓跃臻等研究人员设计了“种植——切除——复发”的过程来模拟和探索索拉菲尼对肝癌术后复发转移的影响。研究发现，索拉菲尼能强力抑制小鼠肝癌切除术后肿瘤的原位复发和腹腔转移，并显著地延长小鼠的生存时间。有意思的是，相比原发肿瘤，索拉菲尼能更加有效的抑制复发肿瘤的生长。进一步的研究表明，术后与肝脏再生相关的生长因子的表达上调所导致的ERK活性的增加提高了肝癌细胞对索拉菲尼的敏感性。这一研究结果为将索拉菲尼应用于早期肝癌的治疗（尤其是早期肝癌术后治疗）提供了有力的实验依据。
该研究课题得到了国家科技部、国家自然科学基金委、中国科学院和上海市科委的资助。（生物谷Bioon.com）
生物谷推荐原文出处：
Hepatology, 53: 483–492. doi: 10.1002/hep.24075
Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model
Yu-Xiong Feng1,?, Tao Wang2,?, Yue-Zhen Deng1,?, Pengyuan Yang3, Jing-Jing Li1, Dong-Xian Guan1, Fan Yao1, Yin-Qiu Zhu1, Ying Qin1, Hui Wang1, Nan Li2, Meng-Chao Wu2, Hong-Yang Wang2, Xiao-Fan Wang3, Shu-Qun Cheng2,*,§, Dong Xie1,4,*
Abstract
Surgical resection is the first-line treatment for hepatocellular carcinoma (HCC) patients with well-preserved liver function. Nevertheless, the rate of postoperative recurrence at 5 years is as high as 70%, and this gravely jeopardizes the therapeutic outcome. Clearly, new approaches are needed for preventing the relapse of this deadly disease. Taking advantage of a luciferase-labeled orthotopic xenograft model of HCC, we examined the role of sorafenib, the first systemic drug approved for advanced HCC patients, in the prevention of HCC recurrence. We found that sorafenib suppressed the development of postsurgical intrahepatic recurrence and abdominal metastasis and consequently led to prolonged postoperative survival of mice in this model. Furthermore, hyperactivity of extracellular signal-regulated kinase signaling caused by elevated levels of growth factors associated with postoperative liver regeneration enhanced the sensitivity of HCC cells to sorafenib; this provides a plausible explanation for the observation that recurrent tumors are more responsive to growth inhibition by sorafenib. Conclusion: Our results strongly suggest that by effectively reducing postoperative recurrence, sorafenib has a potential application in early-stage HCC patients who have undergone hepatectomy with curative intention.
