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

Leuk Res. 2011 Jun;35(6):787-92. doi: 10.1016/j.leukres.2010.11.016. Epub 2011 Jan 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Imidazoles / pharmacology*
  • 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 Antitumor Assays / methods*

Substances

  • Antineoplastic Agents
  • Birc5 protein, mouse
  • Imidazoles
  • Inhibitor of Apoptosis Proteins
  • Naphthoquinones
  • Repressor Proteins
  • Survivin
  • YM 155