肝癌是嚴(yán)重影響人類健康的疾病，居世界腫瘤相關(guān)死因的第三位,。手術(shù)切除是目前肝癌治療的首選方法，但是肝癌術(shù)后的5年復(fù)發(fā)率高達(dá)75％以上,，嚴(yán)重制約了手術(shù)的療效,。因此，探尋能有效預(yù)防和抑制肝癌術(shù)后復(fù)發(fā)的方法是提高肝癌治療質(zhì)量的關(guān)鍵,。
索拉菲尼（Sorafenib）是第一個(gè)用于治療晚期肝癌的口服藥物,。通過抑制細(xì)胞內(nèi)多種絲/蘇氨酸激酶和酪氨酸激酶（如B-Raf和VEGFR等）的活性，索拉菲尼能抑制腫瘤細(xì)胞生長和血管生成,。但是,，尚不清楚索拉菲尼能否在通過手術(shù)治療的早期肝癌抑制術(shù)后復(fù)發(fā)和轉(zhuǎn)移。
1月27日,，知名肝臟病研究期刊 Hepatology在線發(fā)表了上海生科院營養(yǎng)所謝東研究組與第二軍醫(yī)大學(xué)合作的關(guān)于索拉菲尼在早期肝癌治療中的作用的最新研究結(jié)果,。利用熒光素酶標(biāo)記的異種原位移植（Orthotopic Xenograft）肝癌小鼠模型，馮宇雄,、王濤和鄧躍臻等研究人員設(shè)計(jì)了“種植——切除——復(fù)發(fā)”的過程來模擬和探索索拉菲尼對肝癌術(shù)后復(fù)發(fā)轉(zhuǎn)移的影響,。研究發(fā)現(xiàn)，索拉菲尼能強(qiáng)力抑制小鼠肝癌切除術(shù)后腫瘤的原位復(fù)發(fā)和腹腔轉(zhuǎn)移,，并顯著地延長小鼠的生存時(shí)間,。有意思的是，相比原發(fā)腫瘤,，索拉菲尼能更加有效的抑制復(fù)發(fā)腫瘤的生長,。進(jìn)一步的研究表明，術(shù)后與肝臟再生相關(guān)的生長因子的表達(dá)上調(diào)所導(dǎo)致的ERK活性的增加提高了肝癌細(xì)胞對索拉菲尼的敏感性,。這一研究結(jié)果為將索拉菲尼應(yīng)用于早期肝癌的治療（尤其是早期肝癌術(shù)后治療）提供了有力的實(shí)驗(yàn)依據(jù),。
該研究課題得到了國家科技部、國家自然科學(xué)基金委,、中國科學(xué)院和上海市科委的資助,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
