Down-regulation of Mcl-1 with antisense technology alters the effect of various cytotoxic agents used in treatment of squamous cell carcinoma of the head and neck

  • Authors:
    • Christiane Skoda
    • Boban M. Erovic
    • Volker Wachek
    • Laurenz Vormittag
    • Fritz Wrba
    • Helga Martinek
    • Gregor Heiduschka
    • Philipp Kloimstein
    • Edgar Selzer
    • Dietmar Thurnher
  • View Affiliations

  • Published online on: June 1, 2008     https://doi.org/10.3892/or.19.6.1499
  • Pages: 1499-1503
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Abstract

Antisense oligonucleotides have recently been identified as new anticancer agents. Since human head and neck cancer cells highly express the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1), the aim of this study was to explore the efficacy of the Mcl-1 suppression in combination with various cytotoxic agents in the head and neck cancer cell line SCC9. After oligonucleotide transfection and/or treatment with cisplatin, 5-fluorouracil (5-FU), gemcitabine, paclitaxel or cetuximab, proliferation assays were performed to determine cell viability. The expression patterns of Mcl-1, Bax and Bak were assessed by Western blot analysis and the apoptotic cells were determined by immunohistochemistry using the M30 antibody. A combined Mcl-1 antisense oligonucleotide treatment with paclitaxel, cetuximab and gemcitabine led to a significant reduction in the viable cells. However, the combination with cisplatin and 5-FU showed only moderate synergistic cytotoxic effects. According to the cytotoxic data, distinct apoptosis rates were observed after the combined treatment with the different substances. Western blot analysis also showed a significant suppression of the Mcl-1 synthesis. Our data show that the Mcl-1 antisense oligonucleotide in combination with certain cytotoxic agents has the potential to significantly decrease cell viability in vitro.

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June 2008
Volume 19 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Skoda C, Erovic BM, Wachek V, Vormittag L, Wrba F, Martinek H, Heiduschka G, Kloimstein P, Selzer E, Thurnher D, Thurnher D, et al: Down-regulation of Mcl-1 with antisense technology alters the effect of various cytotoxic agents used in treatment of squamous cell carcinoma of the head and neck. Oncol Rep 19: 1499-1503, 2008.
APA
Skoda, C., Erovic, B.M., Wachek, V., Vormittag, L., Wrba, F., Martinek, H. ... Thurnher, D. (2008). Down-regulation of Mcl-1 with antisense technology alters the effect of various cytotoxic agents used in treatment of squamous cell carcinoma of the head and neck. Oncology Reports, 19, 1499-1503. https://doi.org/10.3892/or.19.6.1499
MLA
Skoda, C., Erovic, B. M., Wachek, V., Vormittag, L., Wrba, F., Martinek, H., Heiduschka, G., Kloimstein, P., Selzer, E., Thurnher, D."Down-regulation of Mcl-1 with antisense technology alters the effect of various cytotoxic agents used in treatment of squamous cell carcinoma of the head and neck". Oncology Reports 19.6 (2008): 1499-1503.
Chicago
Skoda, C., Erovic, B. M., Wachek, V., Vormittag, L., Wrba, F., Martinek, H., Heiduschka, G., Kloimstein, P., Selzer, E., Thurnher, D."Down-regulation of Mcl-1 with antisense technology alters the effect of various cytotoxic agents used in treatment of squamous cell carcinoma of the head and neck". Oncology Reports 19, no. 6 (2008): 1499-1503. https://doi.org/10.3892/or.19.6.1499