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.
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.
Inoue
Masashi
M
Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Yonago, Japan.
Matsumoto
Sachiko
S
Saito
Hiroaki
H
Tsujitani
Shunichi
S
Ikeguchi
Masahide
M
D000818:Animals; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D015316:Genetic Therapy; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D013997:Time Factors; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D017239:Paclitaxel