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Intraperitoneal administration of a small interfering RNA targeting nuclear factor‐kappa B with paclitaxel successfully prolongs the survival of xenograft model mice with peritoneal metastasis of gastric cancer
Author(s) -
Inoue Masashi,
Matsumoto Sachiko,
Saito Hiroaki,
Tsujitani Shunichi,
Ikeguchi Masahide
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23867
Subject(s) - paclitaxel , medicine , intraperitoneal injection , metastasis , small interfering rna , cancer research , cancer , peritoneal cavity , gene knockdown , cancer cell , nf κb , apoptosis , pharmacology , transfection , chemistry , biology , inflammation , cell culture , surgery , biochemistry , genetics
Activation of nuclear factor‐kappa B (NF‐κB) has been detected in various malignant tumors, including gastric carcinoma, and is associated with tumor growth, metastasis, resistance to chemotherapeutic agents and poor prognosis. Therefore, NF‐κB is a potential target for antitumor therapy. In this study, we used a small interfering RNA (siRNA) to knockdown NF‐κB p65 expression and determined whether intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel was effective for treating peritoneal metastasis of gastric cancer. Western blot analysis revealed that NF‐κB p65 expression was diminished by NF‐κB p65 siRNA. Apoptotic cells were increased after transfection of NF‐κB p65 siRNA compared with control siRNA in the treatment with paclitaxel. In a murine xenograft model, abundant fluorescence was observed on the surface of intraperitoneal nodules of gastric cancer after siRNA administration. Moreover, intraperitoneal administration of NF‐κB p65 siRNA reduced NF‐κB expression in intraperitoneal nodules of gastric cancer. Finally, mice treated by intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel survived for a significantly longer time than mice treated by intraperitoneal administration of paclitaxel alone ( p = 0.0002). Taken together, the present results demonstrate that intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel inhibited cancer growth in mice with peritoneal metastasis of gastric cancer. Therefore, intraperitoneal administration of NF‐κB p65 siRNA and paclitaxel may provide a breakthrough in the treatment of peritoneal metastasis of gastric cancer. © 2008 Wiley‐Liss, Inc.