Antitumor effects of YM155, a novel survivin suppressant, against human aggressive non-Hodgkin lymphoma

• Published in: Leukemia research Vol. 35; no. 6; pp. 787 - 792
• Main Authors: Kita, Aya, Nakahara, Takahito, Yamanaka, Kentaro, Nakano, Kenji, Nakata, Mari, Mori, Masamichi, Kaneko, Naoki, Koutoku, Hiroshi, Izumisawa, Nobuyuki, Sasamata, Masao
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2011
• Subjects: Aggressive non-Hodgkin lymphoma; Animals; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Hematology, Oncology and Palliative Medicine; Humans; Imidazoles - pharmacology; Immunohistochemical analysis; Immunohistochemistry; Inhibitor of Apoptosis Proteins - antagonists & inhibitors; Inhibitor of Apoptosis Proteins - genetics; Inhibitor of Apoptosis Proteins - metabolism; Lymphoma, Non-Hodgkin - drug therapy; Lymphoma, Non-Hodgkin - metabolism; Lymphoma, Non-Hodgkin - pathology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Naphthoquinones - pharmacology; Repressor Proteins - antagonists & inhibitors; Repressor Proteins - genetics; Repressor Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Survivin; Treatment Outcome; Xenograft model; Xenograft Model Antitumor Assays - methods; YM155; Survivin; YM155; Apoptosis; Aggressive non-Hodgkin lymphoma; Xenograft model; Immunohistochemical analysis
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2010.11.016

Abstract YM155, a novel small-molecule that down-regulates survivin, exhibits broad, potent antitumor activity against a range of human tumors. We evaluated the activity of YM155 in aggressive non-Hodgkin lymphoma. In a number of diffuse large B-cell lymphoma lines, YM155 exhibited 50% growth inhibition with values between 0.23 and 3.9 nM. Within in vivo xenograft models, continuous infusion of YM155 eradicated large, established subcutaneous WSU-DLCL-2 and Ramos tumors, with sustained efficacy observed through 4 cycles of YM155 therapy. YM155 increased survival significantly versus rituximab in disseminated Ramos models. This study suggests that YM155 may represent an effective treatment for aggressive lymphomas.