bcl-2 Antisense Therapy Chemosensitizes Human Melanoma in SCID Mice

Nat Med. 1998 Feb;4(2):232-4. doi: 10.1038/nm0298-232.

Abstract

Malignant melanoma is a prime example of cancers that respond poorly to various treatment modalities including chemotherapy. A number of chemotherapeutic agents have been shown recently to act by inducing apoptosis, a type of cell death antagonized by the bcl-2 gene. Human melanoma expresses Bcl-2 in up to 90% of all cases. In the present study we demonstrate that bcl-2 antisense oligonucleotide treatment improves the chemosensitivity of human melanoma grown in severe combined immunodeficient (SCID) mice. Our findings suggest that reduction of Bcl-2 in melanoma, and possibly also in a variety of other tumors, may be a novel and rational approach to improve chemosensitivity and treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / drug effects
  • Actins / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Dacarbazine / pharmacology
  • Female
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / genetics*
  • Mice
  • Mice, SCID
  • Neoplasm Transplantation
  • Oligonucleotides, Antisense / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Transplantation, Heterologous

Substances

  • Actins
  • Antineoplastic Agents
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • Dacarbazine