Xiong Ju, Wu Jin-Sheng, Mao Shan-Shan, Yu Xiang-Nan, Huang Xiao-Xi
Department of General Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, P.R. China.
Department of Oncology, Hainan Nonken Nada Hospital, Danzhou, Hainan 571700, P.R. China.
Oncol Rep. 2016 Sep;36(3):1483-90. doi: 10.3892/or.2016.4968. Epub 2016 Jul 22.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Src is involved in multiple processes of cancer metastasis; however, its significance in HCC is not well defined. In the present study, overexpression of Src phosphorylation (Y416) was observed in the highly metastatic MHCC97H cell line; additionally, through inhibition of Src kinase activation, HCC cell proliferation, migration, invasion and colony formation were significantly reduced in vitro. Tumour growth was not affected in the orthotopic xenograft HCC model, but the metastasic potential was inhibited as revealed by reduced lung metastasic foci after administration of saracatinib. Phosphorylation level of Src pathway signalling molecules, such as Src, FAK and Stat3, were also reduced in vitro and in vivo, as a result of the anti-metastasic effects caused by saracatinib treatment. In conclusion, we demonstrated the pro-metastasic role of Src in HCC, and further experiments suggest the use of the Src inhibitor in combination with cytotoxic agents and other anticancer treatments to improve HCC prognosis.
肝细胞癌（HCC）是全球癌症相关死亡的第三大主要原因。Src参与癌症转移的多个过程；然而，其在HCC中的意义尚未明确界定。在本研究中，在高转移性MHCC97H细胞系中观察到Src磷酸化（Y416）的过表达；此外，通过抑制Src激酶激活，HCC细胞的增殖、迁移、侵袭和集落形成在体外显著减少。在原位异种移植HCC模型中，肿瘤生长未受影响，但在给予萨拉卡替尼后，肺转移灶减少，表明转移潜能受到抑制。由于萨拉卡替尼治疗产生的抗转移作用，Src途径信号分子（如Src、FAK和Stat3）的磷酸化水平在体外和体内也降低。总之，我们证明了Src在HCC中的促转移作用，进一步的实验表明，Src抑制剂与细胞毒性药物和其他抗癌治疗联合使用可改善HCC的预后。
