TGFβ1 Induces EMT In Pancreatic Cancer Cell Lines And Their Related Mechanism Research

Currently, pancreatic cancer is one of the diseases which cause serious damage to human health. In recent years, its incidence has obviously increased and the fatality rate is in fourth of all the cancer.90% of pancreatic cancer patients have metastasized when they were firstly diagnosed. Invasion and metastasis of pancreatic cancer which cause exacerbations and threat life is one of the main features. Through invasion and metastasis, pancreatic tumor cells destroyed the surrounding normal structures and broke away from the primary site and distributed in the surrounding tissue and clearance, and through various means of transport and arrived in discontinuous organizations to grow continualy. The lack of pancreatic capsular and the influence of rich lymph and blood supply made speed development of pancreatic cancer. It often spread from the local of peripancreatic, peritoneal and duodenum and developed into systemic metastasis of liver, lung and many other organs and lost the opportunity to surgery. Therefore, the main method is chemotherapy for pancreatic cancer at present.With the further study of mechanism of tumorigenesis from the experts and scholars, significant progress has been made in the molecular targeted therapy and clinical application was wider in recent years. Years of clinical practice has proved the correctness and feasibility of molecular target therapy. But, at present the pathogenesis of pancreatic cancer and mechanism of tumor metastasis is not fully clear and the targeted therapies for pancreatic cancer and its acting site is not clear. Further study for the mechanism of enhanced invasion and metastasis ability of pancreatic cancer has important clinical significance for the development of targeted drugs and site selection.Transforming growth factor beta 1(TGFβ1) is a kind of functional peptides cytokines and their receptors distributed in almost all organizations which can regulate cell growth, epithelial-to-mesenchymal transition (EMT), invasion and metastasis and plays major roles in tumorigenesis. In the process of EMT, TGFβ1 can mediate the expression of multiple genes of Snail family which is a kind of nuclear transcription factor, thereby adjusting the connection structure between the epithelial cells. But in pancreatic cancer cell line SW1990, TGF beta 1 in the induction of EMT and the related mechanism research is less currently.Aim:To explore TGFβ1 inducing EMT in human pancreatic cancer cell lines and their related mechanism.Method:With TGFβ1 acting on human pancreatic cancer cell line SW1990, we detect the expression level of CDH1 (encoding E-cadherin) and other EMT related genes. And using Trichostatin A (TsA) which is the inhibitor of histonedeacetylase (HDAC) and demethylating agent 5’-Aza-2’-deoxycytidine (5-Aza) as well as the related gene of small interfering RNA (siRNA) acting on human pancreatic cancer cell line SW1990, we detect changes in the level of CDH1 expression.Result:With TGFβ1 acting on human pancreatic cancer cell line SW1990, the mRNA expression of CDH1 decreased (P< 0.05); the mRNA expression of CDH2 (encoding E-cadherin) increased (P< 0.05); the mRNA expression of Snail increased significantly (P < 0.01), while the mRNA expression of HDAC1 and HDAC2 have no significant changes (P> 0.05). Using TGFβ1, TsA,5-Aza and the related gene of siRNA acting on human pancreatic cancer cell line SW1990, group TGFβ1+TsA compared with group TGFβ1, the mRNA expression of CDH1 increased (P<0.05); group TGFβ1+5-Aza compared with group TGFβ1, the mRNA expression of CDH1 have no significant difference (P> 0.05); group TGFβ1+Snail-siRNA compared with group TGFβ1, the mRNA expression of CDH1 increased (P< 0.05); group TGFβ1+HDAC1-siRNA compared with group TGFβ1, the mRNA expression of CDH1 have no significant difference (P> 0.05); group TGFβ1+HDAC2-siRNA compared with group TGFβ1, the mRNA expression of CDH1 increased (P< 0.05).Conclusion:(1) TGFβ1 can induce EMT in human pancreatic cancer cell line SW1990. (2) HDAC2 and Snail play important roles in the down-regulation of E-cadherin in human pancreatic cancer cell line SW1990 and it may be the promising targets for preventing tumor development.