An I kappa B kinase 2 inhibitor IMD-0354 suppresses the survival of adult T-cell leukemia cells

作者：Uota Shin; Dewan Md Zahidunnabi; Saitoh Yasunori; Muto Susumu; Itai Akiko; Utsunomiya Atae; Watanabe Toshiki; Yamamoto Naoki; Yamaoka Shoji^*

来源：CANCER SCIENCE, 2012, 103(1): 100-106.

DOI：10.1111/j.1349-7006.2011.02110.x

Adult T-cell leukemia (ATL) is a fatal T-cell malignancy associated with human T-cell leukemia virus type I infection. The aberrant expression of nuclear factor-kappa B (NF-kappa B) is considered to contribute to the malignant phenotype and chemo-resistance of ATL cells. Because of the poor prognosis of ATL, the development of new therapeutic strategies is direly needed. In the present study, we show that an I kappa B kinase 2 (IKK2) inhibitor, IMD-0354, efficiently inhibits the survival of CD4(+) CD25(+) primary ATL cells and prevents the growth of or induces apoptosis of patient-derived ATL cell lines. Assays of transcription with integrated forms of reporter genes revealed that IMD-0354 suppresses NF-kappa B-dependent transcriptional activity. Moreover, the daily administration of IMD-0354 prevents the growth of tumors in mice inoculated with ATL cells. Our results suggest that targeting IKK2 with a small molecule inhibitor, such as IMD-0354, is an attractive strategy for the treatment of ATL. (Cancer Sci 2012; 103: 100-106)

• 出版日期2012-1
• 单位河北医科大学