Hu Chi-Tan, Wu Jia-Ru, Cheng Chuan-Chu, Wu Wen-Sheng
Research Centre for Hepatology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan.
Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 970, Taiwan.
Cancers (Basel). 2017 May 26;9(6):58. doi: 10.3390/cancers9060058.
The poor prognosis of hepatocellular carcinoma (HCC), one of the most devastating cancers worldwide, is due to frequent recurrence and metastasis. Among the metastatic factors in the tumor microenvironment, hepatocyte growth factor (HGF) has been well known to play critical roles in tumor progression, including HCC. Therefore, c-Met is now regarded as the most promising therapeutic target for the treatment of HCC. However, there are still concerns about resistance and the side effects of using conventional inhibitors of c-Met, such as tyrosine kinase inhibitors. Recently, many alternative strategies of c-Met targeting have been emerging. These include targeting the downstream effectors of c-Met, such as hydrogen peroxide-inducible clone 5 (Hic-5), to block the reactive oxygen species (ROS)-mediated signaling for HCC progression. Also, inhibition of endosomal regulators, such as PKCε and GGA3, may perturb the c-Met endosomal signaling for HCC cell migration. On the other hand, many herbal antagonists of c-Met-dependent signaling, such as saponin, resveratrol, and LZ-8, were identified. Taken together, it can be anticipated that more effective and safer c-Met targeting strategies for preventing HCC progression can be established in the future.
肝细胞癌（HCC）是全球最具毁灭性的癌症之一，其预后较差是由于频繁复发和转移。在肿瘤微环境的转移因素中，肝细胞生长因子（HGF）在包括HCC在内的肿瘤进展中发挥关键作用，这一点已广为人知。因此，c-Met现在被认为是治疗HCC最有前景的治疗靶点。然而，对于使用传统的c-Met抑制剂（如酪氨酸激酶抑制剂）的耐药性和副作用仍存在担忧。最近，许多靶向c-Met的替代策略不断涌现。这些策略包括靶向c-Met的下游效应器，如过氧化氢诱导克隆5（Hic-5），以阻断活性氧（ROS）介导的HCC进展信号。此外，抑制内体调节因子，如蛋白激酶Cε（PKCε）和高尔基体相关γ-适应蛋白3（GGA3），可能会扰乱c-Met内体信号传导，从而影响HCC细胞迁移。另一方面，人们还发现了许多依赖c-Met信号传导的草药拮抗剂，如皂苷、白藜芦醇和LZ-8。综上所述，可以预见，未来能够建立更有效、更安全的靶向c-Met策略来预防HCC进展。
