Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer
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Jian Ping Du1,2,3,5,*, Lin Li1,2,*, Jun Zheng1,2, Ding Zhang2, Wei Liu1,2, Wei Hong Zheng3, Xiao Song Li1, Ru Cheng Yao1, Fangyu Wang6, Sen Liu3,4 and Xiao Tan1,2,3
1Institute of Hepatopancreatobilary Surgery, China Three Gorges University, Yichang 443003, P.R. China
2The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, P.R. China
3Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Medical School of China Three Gorges University, Yichang 443002, P.R. China
4National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, P.R. China
5Department of Vascular surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, 437100, P.R. China
6College of Life Science and Environment, Hengyang Normal University, Hengyang, 421008, P.R. China
*These authors contributed equally to this work
Jun Zheng, email: [email protected]
Sen Liu, email: [email protected]
Xiao Tan, email: [email protected]
Keywords: pancreatic ductal adenocarcinoma; kallikrein-related peptidase 7; short hairpin RNA; small organic inhibitor; chemotherapy target
Received: August 29, 2017 Accepted: December 01, 2017 Published: January 10, 2018
Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease.
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