Inihibitor of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma

Stephen Maxted Ansell, B. K. Arendt, D. M. Grote, Diane F Jelinek, Anne J Novak, L. E. Wellik, Ellen McPhail, C. F. Bennett, A. Fielding

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Survivin is a member of the inhibitor of apoptosis protein (IAP) family and functions both as an apoptosis inhibitor and a regulator of cell division. Survivin overexpresslon is common in many human tumors and correlates with survival in large cell non-Hodgkin's lymphoma. To evaluate this molecule as a potential therapeutic target in large-cell lymphoma, we evaluated the effect of survivin inhibition both in vitro and in vivo. Using an antisense oligonucleotide (ASO) approach, cell growth was significantly inhibited in the DoHH2, RL and HT lymphoma cell lines. In a lymphoma xenograft model, the development of tumors as well as the growth of established tumors was inhibited in the survivin ASO-treated mice compared to controls. To assess the efficacy of the survivin ASO in combination with other biological agents, we combined the survivin ASO with an anti-CD20 monoclonal antibody, rituximab. The effect of survivin ASO and rituximab in combination was additive in vitro. In vivo, however, suppression of tumor growth with the combination was not significantly superior to controls. We conclude that inhibition of survivin expression is an attractive therapeutic strategy in aggressive non-Hodgkin's lymphomas, and that combining survivin ASO with rituximab may enhance the efficacy of this approach.

Original languageEnglish (US)
Pages (from-to)616-623
Number of pages8
JournalLeukemia
Volume18
Issue number3
DOIs
StatePublished - Mar 2004

Fingerprint

Antisense Oligonucleotides
Non-Hodgkin's Lymphoma
Growth
Lymphoma
Neoplasms
Inhibitor of Apoptosis Proteins
Biological Factors
Heterografts
Cell Division
Monoclonal Antibodies
Apoptosis
Cell Line
Survival
Therapeutics
Rituximab

Keywords

  • Apoptosis
  • Lymphoma
  • Rituximab
  • Survivin
  • Xenograft

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Inihibitor of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma. / Ansell, Stephen Maxted; Arendt, B. K.; Grote, D. M.; Jelinek, Diane F; Novak, Anne J; Wellik, L. E.; McPhail, Ellen; Bennett, C. F.; Fielding, A.

In: Leukemia, Vol. 18, No. 3, 03.2004, p. 616-623.

Research output: Contribution to journalArticle

Ansell, Stephen Maxted ; Arendt, B. K. ; Grote, D. M. ; Jelinek, Diane F ; Novak, Anne J ; Wellik, L. E. ; McPhail, Ellen ; Bennett, C. F. ; Fielding, A. / Inihibitor of survivin expression suppresses the growth of aggressive non-Hodgkin's lymphoma. In: Leukemia. 2004 ; Vol. 18, No. 3. pp. 616-623.
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