RRC ID 62777
Author Kokuryo T, Hibino S, Suzuki K, Watanabe K, Yokoyama Y, Nagino M, Senga T, Hamaguchi M.
Title Nek2 siRNA therapy using a portal venous port-catheter system for liver metastasis in pancreatic cancer.
Journal Cancer Sci
Abstract Nek2 (NIMA-related kinase 2) is a serine-threonine kinase and human homolog of the mitotic regulator NIMA of Aspergillus nidulan. We reported the efficiency of Nek2 siRNA in several cancer xenograft models using cholangiocarcinoma, breast cancer and colorectal cancer. Pancreatic cancer is difficult to treat due to its rapid progression and resistance to chemotherapy. Novel treatments are urgently required to improve survival in pancreatic cancer, and siRNA are a promising therapeutic option. However, finding an in vivo drug delivery system of siRNA remains a major problem for clinical application. In this study, the overexpression of Nek2 was identified in pancreatic cancer cell lines. Nek2 siRNA inhibited tumor growth in a subcutaneous xenograft mouse model of pancreatic cancer, prolonged the survival time in an intraperitoneal xenograft mouse model and efficiently prevented the progression of liver metastasis using a portal venous port-catheter system. Taken together, Nek2 is an effective therapeutic target in pancreatic cancer. An adequate delivery system is considered important in treating advanced pancreatic cancer, such as peritoneal dissemination and liver metastasis. Further investigations are required on the safety and side effects of the portal venous port-catheter system. We hope that Nek2 siRNA will be a novel therapeutic strategy for pancreatic cancer with liver metastasis and peritoneal dissemination.
Volume 107(9)
Pages 1315-20
Published 2016-9-1
DOI 10.1111/cas.12993
PMID 27316377
PMC PMC5021025
MeSH Animals Cell Line, Tumor Cell Movement / genetics Disease Models, Animal Gene Expression Gene Knockdown Techniques Genetic Therapy Humans Liver Neoplasms / pathology Liver Neoplasms / secondary* Liver Neoplasms / therapy Male Mice Mice, Nude NIMA-Related Kinases / genetics* Pancreatic Neoplasms / genetics* Pancreatic Neoplasms / pathology* Portal Vein* RNA Interference RNA, Small Interfering / administration & dosage* RNA, Small Interfering / genetics* Rats Tumor Burden Vascular Access Devices* Xenograft Model Antitumor Assays
IF 4.966
Human and Animal Cells KP4(RCB1005)