Open Access

Synergistic inhibition of the growth of MDA‑MB‑231 cells in triple‑negative breast cancer by salinomycin combined with 17‑AAG and its mechanism

  • Authors:
    • Duo He
    • Bo Wu
    • Juan Du
    • Ling Li
    • Jumei Zhao
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  • Published online on: March 1, 2022     https://doi.org/10.3892/ol.2022.13258
  • Article Number: 138
  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Salinomycin (SAL), a typical ion carrier antibiotic, inhibits tumor growth and metastasis by inducing apoptosis or autophagy in cancer or cancer stem cells and thus overcomes drug resistance. 17‑allylamino‑17‑demethoxygeldanamycin (17‑AAG), a heat shock protein Hsp90 competitive inhibitor, also has a role in inhibiting tumor development. However, their combination on the growth of breast cancer cells and its specific mechanism remains to be elucidated. The present study tested the influence of SAL and 17‑AAG on cell growth, apoptosis and autophagy by MTT assays, Annexin V‑FITC and propidium iodide double staining assay and immunoelectron microscopy. The influence of SAL and 17‑AAG on proteomics was investigated by isobaric tag for relative and absolute quantitation. It was found that SAL combined with 17‑AAG synergistically inhibited the cell growth and induced the apoptosis in a concentration‑dependent manner, with the expression of caspase 3 and Bcl‑2 were decreased while the expression of Bax was increased. In addition, SAL combined with 17‑AAG inhibited autophagy, with the expression of microtubule‑associated protein 1 light chain 3, Beclin1, p62 being decreased. Mechanistically, SAL combined with 17‑AAG synergistically inhibited the reactive oxygen species/JNK signaling pathway. In conclusion, SAL combined with 17‑AAG had a synergistic inhibitory effect on cell growth of breast cancer via inducing apoptosis and inhibiting autophagy. The present study might provide a new strategy for potential clinical application of SAL as a new anti‑tumor drug especially as a drug combination with other molecular targeting therapeutics.
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April-2022
Volume 23 Issue 4

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

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Spandidos Publications style
He D, Wu B, Du J, Li L and Zhao J: Synergistic inhibition of the growth of MDA‑MB‑231 cells in triple‑negative breast cancer by salinomycin combined with 17‑AAG and its mechanism. Oncol Lett 23: 138, 2022
APA
He, D., Wu, B., Du, J., Li, L., & Zhao, J. (2022). Synergistic inhibition of the growth of MDA‑MB‑231 cells in triple‑negative breast cancer by salinomycin combined with 17‑AAG and its mechanism. Oncology Letters, 23, 138. https://doi.org/10.3892/ol.2022.13258
MLA
He, D., Wu, B., Du, J., Li, L., Zhao, J."Synergistic inhibition of the growth of MDA‑MB‑231 cells in triple‑negative breast cancer by salinomycin combined with 17‑AAG and its mechanism". Oncology Letters 23.4 (2022): 138.
Chicago
He, D., Wu, B., Du, J., Li, L., Zhao, J."Synergistic inhibition of the growth of MDA‑MB‑231 cells in triple‑negative breast cancer by salinomycin combined with 17‑AAG and its mechanism". Oncology Letters 23, no. 4 (2022): 138. https://doi.org/10.3892/ol.2022.13258