BcI-xL antisense treatment sensitizes Bcl-xL-overexpressing squamous cell carcinoma cells to carboplatin

Oral Oncol. 2002 Dec;38(8):752-6. doi: 10.1016/s1368-8375(02)00047-7.

Abstract

Carboplatin (CBDCA) has been widely used for the treatment of oral squamous cell carcinoma (SCC). The Bcl-2 family member Bcl-xL has been demonstrated to provide resistance to chemotherapeutic agents including CBDCA. Morpholino Bcl-xL antisense oligonucleotides (oligos) were employed to down-regulate Bcl-xL in CBDCA-resistant (MIT8, MIT16) as well as CBDCA-sensitive (MIT7) SCC cell lines. The oligos were delivered to adherent cells using a scrape-load procedure. The Bcl-xL antisense reduced Bcl-xL levels without altering the level of control actin, suggesting the specificity of this agent. The addition of Bcl-xL antisense oligos substantially prevented the cell growth of both CBDCA-sensitive and-resistant cells. The CBDCA-induced partial prevention of cell growth was further augmented by the addition of the Bcl-xL, but not the control, antisense oligos. The morpholino type Bcl-xL antisense oligos may be useful for the treatment of SCC, especially multidrug-resistant tumors with enhanced Bcl-xL levels.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carboplatin / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Division
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Drug Therapy, Combination
  • Humans
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Oligonucleotides, Antisense / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Treatment Outcome
  • Tumor Cells, Cultured
  • bcl-X Protein

Substances

  • Antineoplastic Agents
  • BCL2L1 protein, human
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Carboplatin