The Effects And Mechanism Of P, P’-DDT On Colon Cancer Cell DLD1 Proliferation And Adhesion

2,2-bis (4-Chlorophenyl)-1,1,1-trichloroethane (p, p’-DDT), is the first widely used organic chlorine pesticide. In the last century, DDT has been intensively used for agriculture and treatment of infectious diseases such as malaria, typhoid. Due to its persistence and environmental toxicity, DDT is banned to use in most countries. DDT, a kind of persistent organic pollutants, exposes to human body through direct contact and food chain, resulting in many adverse effects on human health. Colon cancer is one of the common malignant tumors and the incidence rate presents an upward trend year by year. The causes of colon cancer include genetic factor, environmental factor, food and lifestyle. Recent epidemiological survey found the relationship between DDT exposure and colon cancer development, but the mechanism is still not clear. This study aims to study the effects and mechanism of p, p’-DDT on colon cancer development. The research includes the following several parts:The first part:MTT assay was used for measure the effect of p, p’-DDT on DLD1 cell survival. Effect of p, p’-DDT on Wnt/β-catenin signaling pathway and its downstream target genes were detected by western blotting and RNA interference. Effect of p, p’-DDT on oxidative stress in DLD1 cells was investigated by measuring ROS level and SOD activity. The results showed that p,p’-DDT promotes DLD1 cell proliferation through oxidative stress mediated-Wnt/p-catenin signaling pathway activationg and its downstream target gene c-Myc and cyclin Dl over expression in vitro.The second part:Effect ofp, β-DDT on colon tumor growth was investigated in nude mice model. Wnt/β-catenin signaling pathway and Ki-67 expression was detected by immunohistochemistry and western blotting. Effect of p, p’-DDT on oxidative stress in tumor was detected by measuring SOD activity and GSH contents. The results showed that p, p’-DDT promotes colon tumor growth through oxidative stress mediated-Wnt/β-catenin signaling pathway.The third part:Effect ofp,p’-DDT on cell-cell and cell-matrix adhesion of DLD1 cells was detected by cell aggregation assay and crystal violet staining. Expression of adhesion factors was detected by quantitative real-time PCR and western blotting. The results showed that p, p’-DDT may inhibit cell-cell adhesion of DLD1 cells via downregulating intercellular adhesion molecule E-cadherin expression, p,p’-DDT may promote cell-matrix adhesion of DLD1 cells through upregulating extracellular matrix adhesion factor CD29 expression.In summary,p,p’-DDT promotes colon cancer development by afftecting cell proliferation and cell adhesion.