Inoue M, Matsumoto S, Saito H, Tsujitani S, Ikeguchi M.. 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. Int J Cancer 123: 2696-2701

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Yonago, Japan.
International Journal of Cancer (Impact Factor: 5.09). 12/2008; 123(11):2696-701. DOI: 10.1002/ijc.23867
Source: PubMed


Activation of nuclear factor-kappa B (NF-kappaB) 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-kappaB is a potential target for antitumor therapy. In this study, we used a small interfering RNA (siRNA) to knockdown NF-kappaB p65 expression and determined whether intraperitoneal administration of NF-kappaB p65 siRNA and paclitaxel was effective for treating peritoneal metastasis of gastric cancer. Western blot analysis revealed that NF-kappaB p65 expression was diminished by NF-kappaB p65 siRNA. Apoptotic cells were increased after transfection of NF-kappaB 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-kappaB p65 siRNA reduced NF-kappaB expression in intraperitoneal nodules of gastric cancer. Finally, mice treated by intraperitoneal administration of NF-kappaB 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-kappaB p65 siRNA and paclitaxel inhibited cancer growth in mice with peritoneal metastasis of gastric cancer. Therefore, intraperitoneal administration of NF-kappaB p65 siRNA and paclitaxel may provide a breakthrough in the treatment of peritoneal metastasis of gastric cancer.

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Available from: Shunichi Tsujitani, Nov 20, 2014
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    • "Only a few papers describe non-viral siRNA based strategies to inhibit NF-κB activation in animal models of diseases. Lipid based siRNA-mediated knock-down of p65 via intraperitoneal administration in combination with paclitaxel prolonged survival in a mouse model of peritoneal metastasis of gastric cancer [163], suggesting that this approach may also be beneficial in humans via sensitization of tumor cells to chemotherapy. Recently, it was demonstrated that siRNA-mediated reduction of IKKβ prevented TNFα-induced insulin resistance in human skeletal muscle ex vivo [164], possibly reducing insulin resistance. "
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