The basic study of molecular targeted therapy via pancreatic duct tight junctions by using a novel culture system of human pancreatic duct epithelial cells

本研究采用正常人胰腺导管上皮细胞和癌细胞系。我们对紧密连接分子claudin-4、claudin-18和在胰腺癌中高表达的信号分子PKC进行了基础研究。在人胰腺导管上皮细胞和癌细胞中，紧密连接蛋白-4和-18通过PKCalpha信号转导途径调节。CPE通过claudin-4的细胞毒性作用被认为可用作胰腺癌的新型治疗工具。在任何浓度的CPE下均未观察到细胞毒性，而在胰腺癌细胞中，CPE具有剂量依赖性细胞毒性效应。PKCalpha抑制剂代表通过使用经由密蛋白-4的CPE细胞毒性针对人胰腺癌细胞的潜在治疗剂。

In the present study, using normal human pancreatic duct epithelial cells and cancer cell lines. we investigated the basic study targeting tight junction molecules claudin-4, -18 and a signal molecule PKC that highly expressed in pancreatic cancer. Claudin-4 and -18 were regulated via a PKCalpha signal transduction pathway in both human pancreatic duct epithelial cells and cancer cells. The cytotoxic effects of CPE via claudin-4 are thought to be useful as a novel therapeutic tool for pancreatic cancer. The cytotoxicity was not observed at any concentration of CPE, whereas in pancreatic cancer cells, CPE had a dose-dependent cytotoxic effect. PKCalpha inhibitors represent potential therapeutic agents against human pancreatic cancer cells by the use of CPE cytotoxicity via claudin-4.