Effects Of Anti-tumor Drug Sorafenib On Chick Embryo Development

It is well known that sorafenib could act as the oral anti-cancer drug in clinic since its significantly inhibitive effects on tumor growth and EMT. Its pharmacological effect is mainly based on tumor models in vivo and in vitro, and clinic experinernce. However, these models extis shortcomings more or less. So we want to look for a new model. Since tumor cells and embryonic cells share many similar features, we here employed early developing chick embryo as an in vivo model to investigate the effect of sorafenib on embryo development. Firstly, we disclosed that the development of gastrula chick embryo was distinctly retarded by the exposure of sorafenib. To explore the mechanism of sorafenib-induced retardment of gastrula embryo development, cell proliferation and apoptosis were determined, and uncovered that cell proliferation was inhibited and apoptosis was promoted by the exposure of sorafenib at the gastrula embryo development. Next, gastrula EMT was examined after the treatment of sorafenib since the EMT is the vital step in three germ layer formation, and up-regulation of E-Cadherin and down-regulation of N-cadherin were observed following the treatment of sorafenib, displaying the EMT in gastrulation was restricted by sorafenib treatment. Cell migration is crucial event in the process of gastrulation embryo development, so that mesoderm cell migration was detected with the combination of GFP+ primitive streak tissue transplantation and absence/presence of sorafenib application during gastrula embryo development. The result showed that sorafenib treatment significantly interfered with the normal mesoderm cell migration pattern. In order to reinforce aforementioned experimental evidence, cranial neural crest generation was utilized to determine the effect of sorafenib on EMT and cell migration. Again, we disclosed that sorafenib exposure was able to impaired the generation of neural crest cells, indicating the sorafenib possess the ability to inhibit EMT and cell migration,but in fact the cell migration itself was not affected by sorafenib. In sum, sorafenib exposure could inhibit gastrula embryo development through limiting cell proliferation, EMT and cell migration, suggesting that the pharmacological effect of sorafenib on tumorigenesis might be comprehensive of influence factors as stated in embryonic development above. Sorafenib may be though the MAPK singal pathway to affect the development of the chick embryo. At last, sorafenib could also inhibit the production of blood island.