Screen Anti-ras Oncogene Drug Candidates And Develop Second Generation Kit Thereof

Now mouse has been used as an ordinary model organism to screen anti-cancer drugs, but it is costly and time consuming. Alternatively, it’s efficient to tend to biochemical reactions, and cultured cells in vitro or simple organism such as bacteria, yeast, but data based on reaction in vitro may not be associated with their effects in vivo, especially there are more than one drug targets in the body, the intact animal model can often provide more accurate infomation. C. elegans is able to balance these two aspects better.Let-60 gene in C. elegans and the ras oncogene in human are the homologous genes, while about 30% of human tumors are caused by deregulation of ras gene mutations or increased levels of Ras protein expression. Among designs of anticancer drugs targeting cell signal pathway, Ras/MAPK pathway plays an important role.Here C. elegans MT2124 strain in which the ras gene has mutated was used as a model organism to screen anti-ras oncogene compounds. At first we use the first-generation anti-ras oncogene drug screening kit to evaluate Sodium TanshinonⅡA silate, Curcurmol, Paeonol. Results showed that those compounds do inhibit over expression of ras oncogene. Sodium TanshinonⅡA silate can increase wild-type worm rate from 20% to 70%; the same effect of Curcurmol is from 25%-65%. Based on these studies, the second generation drug screening kit anti-ras oncogene was developed. A was chosen to dye C. elegans, and then results were detected by fluorescence microplate reader, and the novel generation kit conditions were tested on worm number, wild-type proportion, and concentration of A. Accordingly, we developed the second- generation drug screening kit, and testified the second-generation drug screening kit with Etoposide and Sorafenib. Compared with the first-generation kit, second-generation kit is accurate, simple to operate, labor saving, does not require professional training, so it will be more widely used. Furthermore, we researched cooperative effect between Curcurmol and RBS against over activation of ras oncogene with the second generation of drug screening kit.