In cancer (NSCLC), overexpression of HGF receptor proteins has been frequently demonstrated [18,19] and has been shown to be associated with adverse clinical outcomes in patients. Studies have shown that cMET protein expression is increased in NSCLC lung tumors with ALK gene rearrangement [20], and gene amplification is uncommon in cancer. Amplified cMET protein expression may be the result of the transcription factor ETS2, which is often down-regulated in cancer [21].

In cancer, HGF has also been shown to interfere with EGF tyrosine kinase activation, leading to induced resistance to EGFR inhibitor therapy [22]. Therefore, the combination of MET tyrosine kinase inhibitors (TKI) and EGF TKI is considered to be an effective new combination to overcome the acquired resistance of TGF TKI in cancer [23]. This has indeed been demonstrated in in vitro studies, where the small cMET inhibitor E7050 blocks the Met/Gb1/ PI3K /Akt pathway in vitro. Reversible, irreversible, and mutation-selective EGFR-TKI resistance induced by exogenous and/or endogenous HGF in EGFR-mutant cancer cell lines can be circumvented [24]. Notably, HGF positive serum is a predictor of negative response to gefitinib therapy in advanced NSCLC patients with wild-type EGFR [25,26]. Serum HGF levels have been shown to be associated with disease progression and overall survival, and interestingly, this is even more true when EGFR status is considered [27].

Overexpression of cMET protein was observed in more than half of small cell lung cancer (SCLC) cancers, and patients with cMET phosphorylated small cell lung cancer tumors had significantly poorer overall survival (132 and 287 days, respectively, for patients with cMET phosphorylated and non-phosphorylated tumors, p<0.001) [28]. Circulating HGF (cHGF) has been found to be a routine feature in cancer patients and is considered a useful biomarker for the selection of HGF/ CMEt-based targeted therapies [29,30]. Cancer may attract neutrophils to release their HGF stores and promote the local microenvironment for cancer progression [31].

Previous reports have shown that Yangzhengxiao has a profound effect on cancer cell migration as well as on endothelial cell migration, suggesting that the drug is an important regulator of cell movement and a potential therapeutic target [32,33]. HGF is one of the most powerful kinogen (motion-stimulating cytokine), which is abnormally expressed in cancer along with the HGF receptor cMET. In this study, we sought to investigate the effects of Yangzhengxiao on lung cancer cell migration, invasion, and cell adhesion, especially in the context of HGF stimulation. In this context, the degree of activation/phosphorylation of the HGF receptor was also investigated to interpret whether and how the elimination of Yang syndrome affects the HGF/cMET complex. This study also investigated the effect of nourishing and eliminating accumulation on the growth of lung tumors in vivo. This paper reports that Yangzheng Xiaoyu can inhibit the function and growth of lung cancer cells in vivo and in vitro. Yangzheng Xiaoji for cancer also influenced HGF- and HGF/ EGF-induced cell migration of lung cancer cells and phosphorylation of the HGF receptor cMET.