Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 14678
© 2008 American Society of Clinical Oncology

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Abstract

Intraperitoneal administration of small interfering RNA targeting nuclear factor kappa B with paclitaxel successfully prolong the survival of murine xenograft with peritoneal metastasis of gastric cancer

Tottori University, Yonago, Japan

14678

Background: Activation of nuclear factor-kappa B (NF-B) is associated with increased tumor growth, metastasis, resistance to chemotherapeutic agents and poor prognosis. As such, NF-B is a potential target for antitumor therapy. We invesigated whether intraperitoneal administration of NF-B p65 siRNA and paclitaxel was effective in the treatment of peritoneal metastasis of gastric cancer. Methods: NF-B p65 expression were evaluated by western blot. Apoptosis were evaluated cell cycle analysis and Hoechst staining. siRNA transfection were evaluated immunofluorescence microscopy and immunohistochemistry. Murine xenograft model were received i.p.injection of a single suspension of MKN1 or MKN45. Results: <in vitro>NF-B p65 normally resides in the cytoplasm and is upregulated in the nucleus in response to paclitaxel. NF-B p65 expression was diminished by NF-B p65 siRNA. Pre-G1 cells, corresponding to apoptotic cells, increased after transfection of NF-B p65 siRNA compared with control siRNA in the treatment of paclitaxel. Hoechst 33258 staining showed exclusive apoptosis of MKN-45 after treatment of paclitaxel and NF-B p65 siRNA. <In vivo>Abundant fluorescence was demonstrated in the surface of intraperitoneal nodules of gastric cancer when the siRNA/liposome complex was administered. And, NF-B expression was reduced mainly in the surface of intraperitoneal nodules where siRNA was transfected when mice were treated with NF-B p65 siRNA/liposome. Although equivalent numbers of cancer cells were injected, cancer growth rates differed among the treatment groups.NF-B p65 siRNA/liposome and paclitaxel treated group tend to be inhibited the growth than other groups. Survival of mice treated NF-BsiRNA/liposome and paclitaxel was significantly prolonged for all treatment groups compared with other groups. Conclusions: Intraperitoneal administration of NF-B p65 siRNA and paclitaxel inhibited cancer growth in mice with peritoneal metastasis of gastric cancer. Therefore, intraperitoneal administration of NF-B p65 siRNA and paclitaxel might cause a breakthrough in the treatment of peritoneal metastasis of gastric cancer.

No significant financial relationships to disclose.