Nek2 siRNA therapy using a portal venous port-catheter system for liver metastasis in pancreatic cancer.
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.
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. kokuryoh@med.nagoya-u.ac.jp.|Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan. kokuryoh@med.nagoya-u.ac.jp.
Toshio
T
Kokuryo
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shigeru
S
Hibino
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.|Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kazushi
K
Suzuki
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Katsutaka
K
Watanabe
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yukihiro
Y
Yokoyama
Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Masato
M
Nagino
Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takeshi
T
Senga
Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Michinari
M
Hamaguchi
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000072379:NIMA-Related Kinases / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D011169:Portal Vein; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D051381:Rats; D047368:Tumor Burden; D062666:Vascular Access Devices; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases
Liver metastasis; Nek2; pancreas cancer; portal venous port-catheter system; siRNA