A molecular targeting against nuclear factor‐κB, as a chemotherapeutic approach for human malignant mesothelioma. (10th February 2014)

• Record Type: Journal Article
• Authors: Nishikawa, Sho; Tanaka, Akane; Matsuda, Akira; Oida, Kumiko; Jang, Hyosun; Jung, Kyungsook; Amagai, Yosuke; Ahn, Ginae; Okamoto, Noriko; Ishizaka, Saori; Matsuda, Hiroshi
• Is Part Of: Cancer medicine. Volume 3:Number 2(2014:Apr.)
• Page Start: 416
• Page End: 425
• Publication Date: 2014-02-10
• Subjects: 616.994005
• DOI: 10.1002/cam4.202
• Languages: English
• ISSNs: 2045-7634

Abstract

<abstract abstract-type="main" id="cam4202-abs-0001"> <title>Abstract</title> <p>Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor‐<italic>κ</italic>B (NF‐<italic>κ</italic>B) pathway contributes to malignant transformation of various types of cells, we explored NF‐<italic>κ</italic>B activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF‐<italic>κ</italic>B inhibitor, IMD‐0354. NF‐<italic>κ</italic>B was constantly activated in MSTO‐211H, NCI‐H28, and NCI‐H2052 cells, and the proliferation of these cell lines was inhibited by IMD‐0354. D‐type cyclins were effectively suppressed in mixed tissue type MSTO‐211H, leading to cell cycle arrest at sub G<sub>1</sub>/G<sub>1</sub> phase. IMD‐0354 reduced cyclin D3 in both epithelial tissue type NCI‐H28 and sarcomatoid tissue type NCI‐H2052. In a sphere formation assay, IMD‐0354 effectively decreased the number and diameter of MSTO‐211H spheres. Preincubation of MSTO‐211H cells with IMD‐0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD‐0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO‐211H cells. These results indicate that a targeted drug against NF‐<italic>κ</italic>B might have therapeutic efficacy in the treatment of human malignant mesothelioma.</p> </abstract>