Chemosensitization of T-47D breast carcinoma cells to TRAIL and Fas receptor-induced killing

Anticancer Res. Mar-Apr 2002;22(2A):673-6.

Abstract

Background: Although chemotherapeutic agents are known to sensitize some tumour types to killing through cell surface death receptors for Fas ligand and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), chemosensitization of breast carcinoma cells has not yet been explored.

Materials and methods: Mitochondrial thiazole tetrazolium assays were used to measure changes in MCF-7 and T-47D breast carcinoma cell viability. Semiquantitative RT-PCR was used to determine Fas and TRAIL receptor mRNA expression.

Results: Treatment with suboptimal concentrations of etoposide or doxorubicin rendered T-47D cells sensitive to anti-Fas antibody or TRAIL, consistent with Fas and TRAIL-R1 mRNA expression by T-47D cells following drug treatment. In contrast, neither drug sensitized MCF-7 cells to TRAIL- or anti-Fas antibody, most likely due to diminished Fas and TRAIL-R1 expression following drug treatment.

Conclusion: These findings suggest that some breast carcinomas may respond favorably to a combination of chemotherapy and immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Doxorubicin / pharmacology
  • Drug Synergism
  • Etoposide / pharmacology
  • Humans
  • Membrane Glycoproteins / pharmacology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*
  • fas Receptor / biosynthesis
  • fas Receptor / genetics
  • fas Receptor / immunology
  • fas Receptor / physiology*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Membrane Glycoproteins
  • RNA, Messenger
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Etoposide
  • Doxorubicin