BcI-xL antisense treatment sensitizes Bcl-xL-overexpressing squamous cell carcinoma cells to carboplatin.
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.
Itoh
M
M
Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-0022, Japan.
Noutomi
T
T
Chiba
H
H
Mizuguchi
J
J
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D016190:Carboplatin