The Preventive Effect And Related Mechanism Of Merfotmin On Cholangiocarcinoma

Cholangiocarcino,which is originated from biliary tract,is often diagnosed at advanced stages and is characterized by high morbidit and poor prognosis.At present,completely resection is the only way to improve patients survival.Therefore,it is significant to prevent and find new therapeutic target for decrease the morbidity and mortality rates.Metformin,as a traditional hypoglycemic agent,is involved in anti-tumor recently.In a retrospective study,researchers found that compared with Type Two diabetics treated with metformin,diabetics treated with other hypoglycemic had higher risk of tumor.we aimed at building rat-cholangiocaricino model,evaluating preventive effect of metformin and finding molecular biological changes within this progress.We use Thioacetamide(TAA)to build cholangiocaricina model.Briefly,rats in experimental group were treated with TAA and metformin,while in control group were treated with TAA only.Livers and blood were harvested and examined at the corresponding time points to evaluate the effect of metformin and TAA.Results showed that long-term use of metformin led to a 30% reduction in TAAinduced CCA in all rats and decreased the incidence of tumor nodules in every rat treated with metformin.It proved that metformin was effective to prevent cholangiocarcinoma(CCA)carcinogenesis in some degree.In order to finding molecular biological changes,we analyzed the genetic changes in TAA-induced animal models and CCA cells after merformin treatment.Interestingly,metformin could induce cell cycle arrest and inhibit abnormal expression of multiple proteins essential for CCA.In summary,we constructed a rat-CCA model and confirmed the preventive effect of metformin through this model.In addition,we clarified the genetic changes,which provide a basis for prevention and treatment of cholangiocaricino.