American Association for Cancer Research
Browse
136162_1_supp_2759095_ngcl61.pptx (214.93 kB)

Supplemental Figure 1 from IKKβ Regulates VEGF Expression and Is a Potential Therapeutic Target for Ovarian Cancer as an Antiangiogenic Treatment

Download (214.93 kB)
figure
posted on 2023-04-03, 14:11 authored by Yasuto Kinose, Kenjiro Sawada, Hiroshi Makino, Tomonori Ogura, Tomoko Mizuno, Noriko Suzuki, Tomoyuki Fujikawa, Eiichi Morii, Koji Nakamura, Ikuko Sawada, Aska Toda, Kae Hashimoto, Aki Isobe, Seiji Mabuchi, Tsuyoshi Ohta, Akiko Itai, Ken-ichirou Morishige, Hirohisa Kurachi, Tadashi Kimura

Dose finding in vivo study of IMD-0354.

History

ARTICLE ABSTRACT

The prolongation of progression-free survival (PFS) in patients with advanced ovarian cancer by antiangiogenic therapy has been shown in several clinical trials. However, although an anti-VEGF antibody (bevacizumab) is the only option currently available, its efficacy is limited and it is not cost effective for use in all patients. Therefore, the development of a novel antiangiogenic drug, especially composed of small-molecule compounds, could be a powerful armament for ovarian cancer treatment. As NF-κB signaling has the potential to regulate VEGF expression, we determined to identify whether VEGF expression is associated with NF-κB activation and to investigate the possibility of a novel IKKβ inhibitor, IMD-0354 (IMMD Inc.), as an antiangiogenic drug. Tissue microarrays from 94 ovarian cancer tissues were constructed and immunohistochemical analyses performed. We revealed that IKK phosphorylation is an independent prognostic factor (PFS: 26.1 vs. 49.8 months, P = 0.011), and is positively correlated with high VEGF expression. In in vitro analyses, IMD-0354 robustly inhibited adhesive and invasive activities of ovarian cancer cells without impairing cell viabilities. IMD-0354 significantly suppressed VEGF production from cancer cells, which led to the inhibition of angiogenesis. In a xenograft model, the treatment of IMD-0354 significantly inhibited peritoneal dissemination with a marked reduction of intratumoral blood vessel formation followed by the inhibition of VEGF expression from cancer cells. IMD-0354 is a stable small-molecule drug and has already been administered safely to humans in other trials. Antiangiogenic therapy targeting IKKβ is a potential future option to treat ovarian cancer. Mol Cancer Ther; 14(4); 909–19. ©2015 AACR.

Usage metrics

    Molecular Cancer Therapeutics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC