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The beneficial role of SIRT1 activator on chemo- and radiosensitization of breast cancer cells in response to IL-6

  • Hossein Masoumi
  • Amin Soltani
  • Mahdi GhatrehsamaniEmail author
Original Article
  • 69 Downloads

Abstract

Tumor environmental cytokines, such as IL-6, has a major role in the outcome of radiation and chemotherapy. In this study, we hypothesized that IL-6 mediates its effects via SIRT1 as a protein deacetylase and activator of phosphatidylinositol-3 kinase pathways. In the present study, we evaluated the effects of the novel dual inhibitor of phosphatidylinositol-3 kinase/mammalian target of rapamycin, NVP-BEZ235, and SIRT1 inhibitor and activator plus radiotherapy in breast cancer cells treated with IL-6. Here, IL-6 untreated/pretreated human breast cancer cells were cultured with single or combination of NVP-BEZ235 and/or SIRT1 activator (SRT1720)/inhibitor (EX-527) under radiotherapy condition. After all treatments, the MTT assay and flow cytometry assay were used to explore cell viability and the ability of our treatments in altering cancer stem cells (CSCs) population or cellular death (apoptosis + necrosis) induction. Simultaneous exposure to NVP-BEZ235 and SRT1720 sensitized breast cancer cells to radiotherapy but elevated CSCs. Treatment with IL-6 for 2 weeks significantly decreased CSCs population. Activation of SIRT1 via SRT1720 in combination with NVP-BEZ235 significantly decreased breast cancer cells viability in IL-6 pretreatment cultures. Inhibition of SIRT1 via EX-527 diminished the beneficial effects of IL-6 pretreatment. The combination of NVP-BEZ235 and SRT1720 as a SIRT1 activation could effectively decrease breast cancer cells population and augments the efficacy of radiotherapy.

Keywords

Breast cancer Chemo-radiotherapy Cancer stem cells IL-6 PI3K/AKT/mTOR SIRT1 

Notes

Acknowledgements

We thank the staffs of Cellular and Molecular Research Center, Shahrekord University of Medical Sciences for their help with conducting the study.

Funding

This work was supported by the Shahrekord University of medical science [Grant Numbers 3058 and 2177]

Compliance with ethical standards

Conflict of interest

There is no conflict of interest to declare.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Medical Physics, Faculty of MedicineShahrekord University of Medical SciencesShahrekordIran
  2. 2.Medical Plants Research Center, Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran
  3. 3.Cellular and Molecular Research CenterShahrekord University of Medical SciencesShahrekordIran

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