A Model For Screening Anti-tumor Dauer Genes And Its’ Appliciation

For malignant tumor,conventional treatments are surgical resection,radiation and chemotherapy or comprehensive methods.However,these cytotoxic chemotherapy often bring a lot of side effects to patients,and there is no significant improvement of 5-year survival for patients of malignancy and the quality of life.Tumor-initiating cell is a special sub-group cells that have the characteristics of stem cells;continued proliferation is considered to be the driven factor of multiple steps in the process of tumorigenesis.In clinic,tumor recurrence often occurs after treatment for a long time,however,circulating tumor cells exists,which indicates the tumor stem cells hide in the body for a long time--in a state of dauer,and patients could live long with tumor.Therefore,on the one hand,tumor dormancy could help tumor cells hide,metastasis and recurrence.On the other hand,inducing tumor cells into long-term dormancy probably is a new tumor therapy.At present,inducing tumor cells dormancy to cure tumor has few research and no proper models in vivo/vitro.C.elegans is a classical model,the glp-1 mutation causes germ-line stem cell continue to proliferation,results in a “tumorous”phenotype.And C.elegans is a mature model for dauer research.We combine these features to form a model for screening anti-tumor dauer genes.First of all,in glp-1 mutant elegans,we tested 5 dauer genes in the classic dauer formation and found these dauer genes could significantly extend the lifespan of glp-1 mutant(most notably can extend the mean lifespan 2 times),and decreased the germ-line stem cell number.However,this effect was dauer-independent.So we think that this model may be used in the screening of anti-tumor dauer genes.Finally,we had screened 9 dauer genes which presented anti-tumor effects.In addition,in the process of our research,we also found that knock down pro-1 gene can extend the lifespan through daf-16 in C.elegans.Knock down pro-1 could promote DAF-16 translocation into nucleus,evelate its transcriptional activity,up-regulate its target genes to significantly extend the lifespan in N2,however,have no effect on its physiological activities such as development,thrash,pumping and reproduction.As above,we formed a model for screening anti-tumor dauer genes.We used this model,found new dauer genes decreasing the germ-line stem cell number and extending “tumorous” worms lifespan.These findings will provide clues for our studies on tumor dormancy inducing for tumor therapy,and make it gradually developing into a new method for cancer therapy.