Inhibition of Inhibitor of Nuclear Factor-κB Phosphorylation Increases the Efficacy of Paclitaxel in in Vitro and in Vivo Ovarian Cancer Models

• DOI: 10.1158/1078-0432.ccr-04-0958
• Publication Date: 2005-09-22T00:00:53Z
• Authors: Seiji Mabuchi; Masahide Ohmichi; Yukihiro Nishio; Tadashi Hayasaka; Akiko Kimura; Tsuyoshi Ohta; Jun Kawagoe; Kazuhiro Takahashi; Namiko Yada-Hashi...; Hozumi Seino-Noda; Masahiro Sakata; Teiichi Motoyama; Hirohisa Kurachi; Joseph R. Testa; Keiichi Tasaka; Yuji Murata
• Keywords: LY294002; IκB kinase; IκBα

Abstract We investigated whether inhibition of nuclear factor-κB (NFκB) increases the efficacy paclitaxel in vitro and vivo ovarian cancer models. Treatment paclitaxel-sensitive Caov-3 cells with transiently activated phosphorylation Akt, IκB kinase (IKK), inhibitor NFκB (IκBα). Paclitaxel also caused a transient increase activity, followed by decrease activity. show an association between Akt IKK that induced is blocked treatment phosphatidylinositol 3-kinase (wortmannin or LY294002). Furthermore, interference signaling cascade inhibits induction IκBα activity paclitaxel. Inhibition (BAY 11-7085) attenuated both basal BAY 11-7085 enhanced for up to 24 hours. In addition, decreased viability treated Moreover, increased paclitaxel-induced intraabdominal dissemination production ascites athymic nude mice inoculated intraperitoneally cells. These results suggest induces via 3-kinase/Akt combination therapy would therapeutic