Open Access

Synergistic anticancer effects of ruxolitinib and calcitriol in estrogen receptor‑positive, human epidermal growth factor receptor 2‑positive breast cancer cells

  • Authors:
    • Seung Taek Lim
    • Ye Won Jeon
    • Hongki Gwak
    • Se Young Kim
    • Young Jin Suh
  • View Affiliations

  • Published online on: February 8, 2018     https://doi.org/10.3892/mmr.2018.8580
  • Pages: 5581-5588
  • Copyright: © Lim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Janus kinase (JAK)1 and JAK2 inhibitor, ruxolitinib, and the active form of vitamin D (calcitriol) were previously reported to possess anticancer effects in breast cancer. The present study investigated the combined effects of ruxolitinib and calcitriol on an estrogen receptor (ER)‑positive, human epidermal growth factor receptor 2 (HER2)‑positive, breast cancer cell line. The ER and HER2‑positive MCF7‑HER18 breast cancer cell line was used to investigate the combination effect of ruxolitinib and calcitriol. A bromodeoxyuridine (BrdU) assay was used to investigate cell growth inhibition. The synergism of this combination therapy was examined using the Chou‑Talalay method. Cell cycle analysis was performed by flow cytometry, and apoptosis was evaluated by flow cytometry following Annexin V‑fluorescein isothiocyanate (FITC) and propidium iodide (PI) staining. Alterations in protein expression levels were analyzed by western blotting. The BrdU assay indicated that combination treatment using ruxolitinib and calcitriol produced a synergistic anti‑proliferative effect in MCF7‑HER18 breast cancer cells. Annexin V‑FITC/PI staining and cell cycle analysis identified a synergistic increase in apoptosis and sub‑G1 arrest in the presence of ruxolitinib and calcitriol. Western blot analysis revealed that these synergistic effects of ruxolitinib and calcitriol were associated with reduced protein levels of JAK2, phosphorylated JAK2, c‑Myc proto oncogene protein, cyclin‑D1, apoptosis regulator Bcl‑2 and Bcl‑2‑like protein 1, and with increased levels of caspase‑3 and Bcl‑2‑associated agonist of cell death proteins. The results of the present study demonstrated the synergistic anticancer effects of ruxolitinib and calcitriol in ER and HER2‑positive MCF7‑HER18 breast cancer cells. Based on these findings, ruxolitinib and calcitriol may have potential as a combination therapy for patients with ER and HER2‑positive breast cancer.
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April-2018
Volume 17 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Lim S, Jeon Y, Gwak H, Kim S and Suh Y: Synergistic anticancer effects of ruxolitinib and calcitriol in estrogen receptor‑positive, human epidermal growth factor receptor 2‑positive breast cancer cells. Mol Med Rep 17: 5581-5588, 2018.
APA
Lim, S., Jeon, Y., Gwak, H., Kim, S., & Suh, Y. (2018). Synergistic anticancer effects of ruxolitinib and calcitriol in estrogen receptor‑positive, human epidermal growth factor receptor 2‑positive breast cancer cells. Molecular Medicine Reports, 17, 5581-5588. https://doi.org/10.3892/mmr.2018.8580
MLA
Lim, S., Jeon, Y., Gwak, H., Kim, S., Suh, Y."Synergistic anticancer effects of ruxolitinib and calcitriol in estrogen receptor‑positive, human epidermal growth factor receptor 2‑positive breast cancer cells". Molecular Medicine Reports 17.4 (2018): 5581-5588.
Chicago
Lim, S., Jeon, Y., Gwak, H., Kim, S., Suh, Y."Synergistic anticancer effects of ruxolitinib and calcitriol in estrogen receptor‑positive, human epidermal growth factor receptor 2‑positive breast cancer cells". Molecular Medicine Reports 17, no. 4 (2018): 5581-5588. https://doi.org/10.3892/mmr.2018.8580