Sorafenib Suppresses Postsurgical Recurrence and Metastasis of Hepatocellular Carcinoma in an Orthotopic Mouse Model

被引:113
作者
Feng, Yu-Xiong [2 ]
Wang, Tao [1 ]
Deng, Yue-Zhen [2 ]
Yang, Pengyuan [3 ,4 ]
Li, Jing-Jing [2 ]
Guan, Dong-Xian [2 ]
Yao, Fan [2 ]
Zhu, Yin-Qiu [2 ]
Qin, Ying [2 ]
Wang, Hui [2 ]
Li, Nan [1 ]
Wu, Meng-Chao [1 ]
Wang, Hong-Yang [1 ]
Wang, Xiao-Fan [3 ,4 ]
Cheng, Shu-Qun [1 ]
Xie, Dong [2 ,5 ]
机构
[1] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai 200438, Peoples R China
[2] Chinese Acad Sci, Ctr Canc Res, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China
[3] Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Canc Biol, Durham, NC 27710 USA
[5] Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
SIGNAL-TRANSDUCTION; LIVER-REGENERATION; GROWTH-FACTORS; TUMOR-GROWTH; ANGIOGENESIS; CANCER; EXPRESSION; PATHWAY; PHASE; HEPATECTOMY;
D O I
10.1002/hep.24075
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Surgical resection is the first-fine 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. (HEPATOLOGY 2011;53:483-492)
引用
收藏
页码:483 / 492
页数:10
相关论文
共 32 条
  • [1] Phase II study of sorafenib in patients with advanced hepatocellular carcinoma
    Abou-Alfa, Ghassan K.
    Schwartz, Lawrence
    Ricci, Sergio
    Amadori, Dino
    Santoro, Armando
    Figer, Arie
    De Greve, Jacques
    Douillard, Jean-Yves
    Lathia, Chetan
    Schwartz, Brian
    Taylor, Ian
    Moscovici, Marius
    Saltz, Leonard B.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (26) : 4293 - 4300
  • [2] Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment
    Budhu, Anuradha
    Forgues, Marshonna
    Ye, Qing-Hai
    Jia, Hu-Liong
    He, Ping
    Zanetti, Krista A.
    Kammula, Udai S.
    Chen, Yidong
    Qin, Lun-Xiu
    Tang, Zhao-You
    Wang, Xin Wei
    [J]. CANCER CELL, 2006, 10 (02) : 99 - 111
  • [3] Changes in serum levels of growth factors in healthy individuals after living related liver donation
    Efimova, EA
    Glanemann, M
    Nussler, AK
    Schumacher, G
    Settmacher, U
    Jonas, S
    Nussler, N
    Neuhaus, P
    [J]. TRANSPLANTATION PROCEEDINGS, 2005, 37 (02) : 1074 - 1075
  • [4] Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis
    El-Serag, Hashem B.
    Rudolph, Lenhard
    [J]. GASTROENTEROLOGY, 2007, 132 (07) : 2557 - 2576
  • [5] Liver regeneration .2. Role of growth factors and cytokines in hepatic regeneration
    Fausto, N
    Laird, AD
    Webber, EM
    [J]. FASEB JOURNAL, 1995, 9 (15) : 1527 - 1536
  • [6] Liver Cancer: EphrinA2 Promotes Tumorigenicity Through Rac1/Akt/NF-κB Signaling Pathway
    Feng, Yu-Xiong
    Zhao, Jiang-Sha
    Li, Jing-Jing
    Wang, Tao
    Cheng, Shu-Qun
    Yuan, Yunfei
    Wang, Fudi
    Wang, Xiao-Fan
    Xie, Dong
    [J]. HEPATOLOGY, 2010, 51 (02) : 535 - 544
  • [7] Role of angiogenesis in tumor growth and metastasis
    Folkman, J
    [J]. SEMINARS IN ONCOLOGY, 2002, 29 (06) : 15 - 18
  • [8] FUKUSATO T, 1990, ACTA PATHOL JAPON, V40, P22
  • [9] Gene Expression in Fixed Tissues and Outcome in Hepatocellular Carcinoma
    Hoshida, Yujin
    Villanueva, Augusto
    Kobayashi, Masahiro
    Peix, Judit
    Chiang, Derek Y.
    Camargo, Amy
    Gupta, Supriya
    Moore, Jamie
    Wrobel, Matthew J.
    Lerner, Jim
    Reich, Michael
    Chan, Jennifer A.
    Glickman, Jonathan N.
    Ikeda, Kenji
    Hashimoto, Masaji
    Watanabe, Goro
    Daidone, Maria G.
    Roayaie, Sasan
    Schwartz, Myron
    Thung, Swan
    Salvesen, Helga B.
    Gabriel, Stacey
    Mazzaferro, Vincenzo
    Bruix, Jordi
    Friedman, Scott L.
    Kumada, Hiromitsu
    Llovet, Josep M.
    Golub, Todd R.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (19) : 1995 - 2004
  • [10] Risk factors contributing to early and date phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy
    Imamura, H
    Matsuyama, Y
    Tanaka, E
    Ohkubo, T
    Hasegawa, K
    Miyagawa, S
    Sugawara, Y
    Minagawa, M
    Takayama, T
    Kawasaki, S
    Makuuchi, M
    [J]. JOURNAL OF HEPATOLOGY, 2003, 38 (02) : 200 - 207