The Bcl-2 inhibitor ABT-263 enhances the response of multiple chemotherapeutic regimens in hematologic tumors in vivo

Cancer Chemother Pharmacol. 2010 Oct;66(5):869-80. doi: 10.1007/s00280-009-1232-1. Epub 2010 Jan 23.


Purpose: This study was designed to test the ability of the Bcl-2 family inhibitor ABT-263 to potentiate commonly used chemotherapeutic agents and regimens in hematologic tumor models.

Methods: Models of B-cell lymphoma and multiple myeloma were tested in vitro and in vivo with ABT-263 in combination with standard chemotherapeutic regimens, including VAP, CHOP and R-CHOP, as well as single cytotoxic agents including etoposide, rituximab, bortezomib and cyclophosphamide. Alterations in Bcl-2 family member expression patterns were analyzed to define mechanisms of potentiation.

Results: ABT-263 was additive with etoposide, vincristine and VAP in vitro in the diffuse large B-cell lymphoma line (DLBCL) DoHH-2, while rituximab potentiated its activity in SuDHL-4. Bortezomib strongly synergized with ABT-263 in the mantle cell lymphoma line Granta 519. Treatment of DoHH-2 with etoposide was associated with an increase in Puma expression, while bortezomib upregulated Noxa expression in Granta 519. Combination of ABT-263 with cytotoxic agents demonstrated superior tumor growth inhibition and delay in multiple models versus cytotoxic therapy alone, along with significant improvements in tumor response rates.

Conclusions: Inhibition of the Bcl-2 family of proteins by ABT-263 enhances the cytotoxicity of multiple chemotherapeutics in hematologic tumors and represents a promising addition to the therapeutic arsenal for treatment of these diseases.

Publication types

  • Comparative Study

MeSH terms

  • Aniline Compounds / administration & dosage
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis Regulatory Proteins / genetics
  • Cell Line, Tumor
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / pathology
  • Mice
  • Mice, SCID
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Sulfonamides / administration & dosage
  • Xenograft Model Antitumor Assays


  • Aniline Compounds
  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • PMAIP1 protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfonamides
  • navitoclax