| [Backgrounds]Colon cancer is one of the world's most common malignant tumors,the incidence of which increased year by year in our country.Although Treatment as surgical operation,Internal medicine treatment in continuous innovation,but colon cancer mortality has not been well controlled that associated with its malignant progression.There are many factors affecting the progression of malignant tumors,in addition to genetic factors,environmental factors also can contribute to malignant progression of tumors by inducing chronic stress and other mechanisms,including environmental pollution of heavy metal pollutants.Epidemiological studies suggest that: in heavy metal pollutants,aresnic and cadmium accounted for the most important position.Early studies suggest that heavy metal pollutants As can promote the progression of cancer by inducing EMT mechanisms.And another important pollutant Cd is class I carcinogen that widely distributed in soil,air and water.Cd exposure comes mainly from food,cigarette smoke and industrial pollution.Its biological half-life is long,so it can accumulate toxicity in the body and even cause cancer,but the effects of Cd on tumor progression have not been reported.EMT(epithelial-mesenchymal transition)is the biological processes of epithelial cells transform into the mesenchymal cells phenotype by specific program.EMT play an important role in embryonic development,inflammation,fibrotic diseases,which is also the important driving force of progress in tumor biology.Many studies show that Cd relates to a variety of the development of tumors(lung cancer,prostate cancer,bladder Cancer,kidney cancer,etc),But the molecular mechanisms of cadmium-induced colon carcinogenesis is poorly understood.This article aims to explore the impact of malignant biological behavior on human colon cancer cell lines HCT-116 at environmental pollution concentrations of chronic exposure by Cd,to verify its mechanism whether associated with EMT.To investigate the influence of malignant biological behavior and mechanisms of HCT-116 cells induced by cadmium.This study aims to explore that colon cancer cell lines HCT-116 by chronic induced of Cd at low concentrations,to establish stable cell lines after induction,To observe changes in the malignant behavior of colon cancer cell lines HCT-116,to explore the mechanism whether associates with EMT.[Methods]After HCT-116 cells were treated with cadmium,the changes in cell malignant biological behavior were assessed by MTT assay,colony forming assay,cell adhesion assay,and transwell migration and invasion assays.Western blot was used to detect the expression of E-cadherin,Vimentin,Zinc finger E-box binding homeobox1,MMP-3,MMP-9 and other proteins in cadmium treated cells.[Results]Chronic exposure to cadmium enhanced the malignant biological behavior of HCT-116 cells,and the transformed cells formed mesenchymal-like intercellular junctions.The protein expression of vimentin,MMP3,MMP9 was increased,while the expression of E-cadherin was decreased in a time-dependent manner.Overall,morphological and molecular changes suggested that HCT-116 cells underwent an EMT process after chronic Cd exposure.[Conclusion]The study Indicates that after chronic exposured to Cd at low doses,human colon cancer cell lines HCT-116 became loose connection,adhesion decreased;and Cadmium promotes the malignant biology behavior(the capacity of proliferation,migration,invasion,etc)of the HCT-116 cells.Results indicate that Cadmium enhances the malignant biologic behavior of HCT-116 cells possibly by inducing EMT.Western blot results verified our ideas.With compared the control group,the expression of EMT-related marker E-cadherin was significantly increased while Vimentin decresed.The expression of MMP-3,MMP-9 has increased in varying degrees.And the expression of ZEB1,?-catenin was significantly increased.It showed that exposure to Cd in the environmental pollution concentrations can promote malignant progression of colon cancer HCT-116 cells via EMT. |
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