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S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin

  • Authors:
    • Jin‑Ah Park
    • Hyeon‑Ok Jin
    • Ha‑Na Lee
    • Jin‑Hee Kim
    • In‑Chul Park
    • Woo Chul Noh
    • Yoon Hwan Chang
    • Young Jun Hong
    • Keun‑Chul Kim
    • Jin Kyung Lee

  • View Affiliations

  • Published online on: June 11, 2015     https://doi.org/10.3892/ol.2015.3369
  • Pages: 829-834
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Abstract

Breast cancer cells possess a deregulated apoptotic pathway with increased expression levels of anti‑apoptotic B‑cell lymphoma‑2 (Bcl‑2) family proteins and ribosomal S6 kinase 1 (S6K1) protein activity. Therefore, combined interference of anti‑apoptotic Bcl‑2 family and S6K1 protein expression may be a reasonable therapeutic strategy for the treatment of patients with breast cancer. In the present study, it was identified that the administration of a combination of ABT263 [navitoclax; a Bcl‑2/Bcl‑extra large (Bcl‑xL) inhibitor] and PF4708671 (an S6K1 inhibitor) markedly increased apoptotic cell death in the BT474 breast cancer cells compared with the administration of either agent alone. Furthermore, the downregulation of Bcl‑2/Bcl‑xL and S6K1 with small interfering RNA induced a significant increase in cell death compared with RNA interference of either agent alone. Notably, combination treatment with ABT263 and PF4708671 decreased the expression level of survivin protein, with this ectopic expression of survivin attenuating cell death. Thus, the present study determined that the combined inhibition of Bcl‑2/Bcl‑xL and S6K1 may be a good strategy for treating patients with breast cancer.
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August-2015
Volume 10 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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  • Journal Metrics
  • Impact Factor: 2.5
  • Ranked Oncology
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  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
  • SCImago Journal Rank (SJR): 0.644
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Spandidos Publications style
Park JA, Jin HO, Lee HN, Kim JH, Park IC, Noh WC, Chang YH, Hong YJ, Kim KC, Lee JK, Lee JK, et al: S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin. Oncol Lett 10: 829-834, 2015.
APA
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W.C. ... Lee, J.K. (2015). S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin. Oncology Letters, 10, 829-834. https://doi.org/10.3892/ol.2015.3369
MLA
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W. C., Chang, Y. H., Hong, Y. J., Kim, K., Lee, J. K."S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin". Oncology Letters 10.2 (2015): 829-834.
Chicago
Park, J., Jin, H., Lee, H., Kim, J., Park, I., Noh, W. C., Chang, Y. H., Hong, Y. J., Kim, K., Lee, J. K."S6K1 inhibition enhances the apoptotic cell death of breast cancer cells in response to Bcl‑2/Bcl‑xL inhibition by the downregulation of survivin". Oncology Letters 10, no. 2 (2015): 829-834. https://doi.org/10.3892/ol.2015.3369