Oral Oncology
Volume 38, Issue 8 , Pages 752-756, December 2002

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

  • M Itoh

      Affiliations

    • Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-0022, Japan
  • ,
  • T Noutomi

      Affiliations

    • Department of Oral and Maxillofacial-Surgery, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan
  • ,
  • H Chiba

      Affiliations

    • Department of Oral and Maxillofacial-Surgery, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
  • ,
  • J Mizuguchi

      Affiliations

    • Department of Immunology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-0022, Japan
    • Intractable Disease Research Center, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-0022, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81-3-3351-6141; fax: +81-3-3341-2941

Received 30 May 2002; accepted 19 June 2002.

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.

Keywords:  Antisense, Bcl-xL, Squamous cell carcinoma, CBDCA

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PII: S1368-8375(02)00047-7

doi:10.1016/S1368-8375(02)00047-7

Oral Oncology
Volume 38, Issue 8 , Pages 752-756, December 2002