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

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Yonago, Japan.
International Journal of Cancer (Impact Factor: 5.01). 12/2008; 123(11):2696-701. DOI: 10.1002/ijc.23867
Source: PubMed

ABSTRACT 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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