Gecko protein F2 inhibits tumor angiogenesis by suppressing the VEGF/MAPK/ERK signaling pathway

The anti-tumor clinical effect of traditional Chinese medicine gecko is very prominent. A novel anti-tumor protein component F2 was isolated and purified from geckos by our group, and the aim of this study was to investigate its antitumor effects in vitro and in vivo and its mechanism of action by inhibiting angiogenesis. The proliferation of cells was determined by colony formation assay and MTT assay. The apoptosis of A549 cells was detected by flow cytometry, and the gene expression changes of cells was analyzed by RNA-seq technology. An H22 tumor-bearing mouse model was prepared, the tumor tissue was analyzed by CD31 immunohistochemical staining. The expression levels of target proteins were detected by Western blot. The proliferation of tumor cells A549 and BEL-7402 was significantly inhibited by F2, but the growth of normal cells L02 was not affected. F2 induces apoptosis in A549 cells and inhibits its migration. RNA-seq results showed that F2 significantly inhibited MAPK signaling pathway in A549 and BEL-7402 cells, and the related genes MEK2 and ERK were significantly down-regulated. The zebrafish thrombus model test showed that the extract of gecko has a significant inhibitory effect on thrombus formation in zebrafish. F2 showed a tumor inhibition rate of 42.24% in mice. A decrease in blood vessels around the tumor and in the tumor tissue was observed. The treatment resulted in a significant down-regulation of VEGF and p-ERK expressions, while a significant up-regulation of p-JNK. In conclusion, F2 has significant antitumor activity. One of its mechanisms of action is to suppress angiogenesis in tumor tissue and surrounding tissues by inhibiting the VEGF/ERK/MAP signaling pathway.