RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance

  • Authors:
    • Guo‑Zheng Pan
    • Feng‑Xian Zhai
    • Yin Lu
    • Zhi‑Gang Fang
    • Rui‑Fang Fan
    • Xiang‑Fu Liu
    • Dong‑Jun Lin
  • View Affiliations

  • Published online on: August 5, 2016     https://doi.org/10.3892/or.2016.5005
  • Pages: 1927-1938
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The interaction between bone marrow stromal cells and leukemia cells is critical for the persistence and progression of leukemia, and this interaction may account for residual disease. However, the link between leukemia cells and their environment is still poorly understood. In our study, runt‑related transcription factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and involved in mesenchymal stem cell (MSC)‑mediated protection of leukemia cells from As2O3‑induced apoptosis. We observed induction of RUNX3 expression and the translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells. In K562 chronic myeloid leukemia cells, downregulation of endogenous RUNX3 compromised As2O3‑induced growth inhibition, cell cycle arrest, and apoptosis. In the presence of MSC, As2O3‑induced expression of RUNX3 was reduced significantly and this reduction was modulated by CXCL12/CXCR4 signaling. Furthermore, overexpression of RUNX3 restored, at least in part, the sensitivity of leukemic cells to As2O3. We conclude that RUNX3 plays an important role in As2O3‑induced cellular responses and allows cells to overcome MSC‑mediated drug resistance. Therefore, RUNX3 is a promising target for therapeutic approaches to overcome MSC‑mediated drug resistance.
View Figures
View References

Related Articles

Journal Cover

October-2016
Volume 36 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Pan GZ, Zhai FX, Lu Y, Fang ZG, Fan RF, Liu XF and Lin DJ: RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance. Oncol Rep 36: 1927-1938, 2016
APA
Pan, G., Zhai, F., Lu, Y., Fang, Z., Fan, R., Liu, X., & Lin, D. (2016). RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance. Oncology Reports, 36, 1927-1938. https://doi.org/10.3892/or.2016.5005
MLA
Pan, G., Zhai, F., Lu, Y., Fang, Z., Fan, R., Liu, X., Lin, D."RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance". Oncology Reports 36.4 (2016): 1927-1938.
Chicago
Pan, G., Zhai, F., Lu, Y., Fang, Z., Fan, R., Liu, X., Lin, D."RUNX3 plays an important role in As2O3‑induced apoptosis and allows cells to overcome MSC‑mediated drug resistance". Oncology Reports 36, no. 4 (2016): 1927-1938. https://doi.org/10.3892/or.2016.5005