YangZheng XiaoJi exerts anti-tumour growth effects by antagonising the effects of HGF and its receptor, cMET, in human lung cancer cells

Journal of Translational Medicine

Research

Lucy Satherley¹  Malcolm D. Mason¹  Lin Ye¹  Wen G. Jiang¹  Ping-Hui Sun¹  Hoi P. Weeks¹  Sioned Owen¹  Andrew J. Sanders¹  Fiona Ruge¹  Tracey Martin¹  Jane Lane¹  Cong Wei²  Yong Gao²  Yiling Wu² 

[1] Cardiff University-Peking University Cancer Institute, Cardiff University School of Medicine, Henry Wellcome Building, Heath Park, CF14 4XN, Cardiff, UK;Yiling Medical Research Institute, No. 238 TianShan DaJie, Shijianzhuang, HeBei Province, China;

关键词: Lung cancer;    Tumour model;    YangZheng XiaoJi;    Hepatocyte growth factor;    cMET;    HGF;    Cellular migration;   

DOI  :  10.1186/s12967-015-0639-1

 received in 2014-12-26, accepted in 2015-08-14,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundHepatocyte growth factor (HGF) is a cytokine that has a profound effect on cancer cells by stimulating migration and invasion and acting as an angiogenic factor. In lung cancer, the factor also plays a pivotal role and is linked to a poor outcome in patients. In particular, HGF is known to work in combination with EGF on lung cancer cells. In the present study, we investigated the effect of a traditional Chinese medicine reported in cancer therapies, namely YangZheng XiaoJi (YZXJ) on lung cancer and on HGF mediated migration and invasion of lung cancer cells.MethodsHuman lung cancer cells, SKMES1 and A549 were used in the study. An extract from the medicine was used. Cell migration was investigated using the EVOS and by ECIS. Cell–matrix adhesion and in vitro invasion were assessed. In vivo growth of lung cancer was tested using an in vivo xenograft tumour model and activation of the HGF receptor in lung tumours by an immunofluorescence method.ResultsBoth lung cancer cells increased their migration in response to HGF and responded to YZXJ by reducing their speed of migration. YZXJ markedly reduced the migration and in vitro invasiveness induced by HGF. It worked synergistically with PHA665752 and SU11274, HGF receptor inhibitors on the lung cancer cells both on HGF receptor activation and on cell functions. A combination of HGF and EGF resulted in a greater increase in cell migration, which was similarly inhibited by YZXJ, and in combination with the HGF receptor and EGF receptor inhibitors. In vivo, YZXJ reduced the rate of tumour growth and potentiated the effects of PHA665752 on tumour growth. It was further revealed that YZXJ significantly reduced the degree of phosphorylation of the HGF receptor in lung tumours.ConclusionYZXJ has a significant role in reducing the migration, invasion and in vivo tumour growth of lung cancer and acts to inhibit the migratory and invasive effects induced by HGF and indeed by HGF/EGF. This effect is likely attributed to the inhibition of the HGF receptor activation. These results indicate that YZXJ has a therapeutic role in lung cancer and that combined strategy with methods to block HGF and EGF should be considered.

【 授权许可】

CC BY   
© Jiang et al. 2015