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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Article

Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation

  • Authors:
    • Ping Wang
    • Dan Ma
    • Jishi Wang
    • Qin Fang
    • Rui Gao
    • Weibing Wu
    • Tangsheng Lu
    • Lu Cao
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Affiliated Hospital of Guiyang Medical University, Guiyang 550004, P.R. China, Department of Pharmacy, Affiliated Baiyun Hospital of Guiyang Medical University, Guiyang 550014, P.R. China, School of Pharmacy, Guiyang Medical University, Guiyang 550004, P.R. China
  • Pages: 1317-1327
    |
    Published online on: January 12, 2015
       https://doi.org/10.3892/ijo.2015.2835
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Abstract

Heme oxygenase-1 was reported previously as a resistance target on acute myelocytic leukemia (AML). We found that HO-1 was resistant to 5-azacytidine (AZA) treatment of myelodysplastic syndrome (MDS), and explored further the relative mechanisms. Patient bone marrow mononuclear cells (n=48) diagnosed as different levels of MDS were collected. Cell growth was evaluated by MTT assay; cell cycle and apoptosis were detected by flow cytometry; mRNA expression was assessed by real-time PCR, protein expression was analyzed through western blotting. Methylation was assessed by MSP. The survival time, and weight of mice were recorded. HO-1 overexpression was observed in SKM-1 cells after AZA treatment comparing to other cell lines. The HO-1 expression in MDS patients with high-risk was higher than in low-risk patients. After HO-1 was silenced by lentivirus-mediated siRNA, the proliferation of SKM-1 cells was effectively inhibited by low concentration AZA, and the cell cycle was arrested in the G0/G1 phase. Upregulation of p16 and changing of p16-relative cell cycle protein was observed after silencing HO-1 in AZA treated SKM-1 cells. In addition, DNMT1 was downregulated following the decrease of HO-1 expression. In vivo, silencing HO-1 inhibited SKM-1 cell growth induced by AZA in a NOD/SCID mouse model. Silencing HO-1 sensitized SKM-1 cells toward AZA, which may be attributed to the influence of HO-1 on AZA-induced p16 demethylation. HO-1 may be one of the targets that enhance the therapeutic effects of AZA on MDS malignant transformation inspiring new treatment methods for high-risk and very high-risk MDS patients in clinical practice.
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Copy and paste a formatted citation
Spandidos Publications style
Wang P, Ma D, Wang J, Fang Q, Gao R, Wu W, Lu T and Cao L: Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation. Int J Oncol 46: 1317-1327, 2015.
APA
Wang, P., Ma, D., Wang, J., Fang, Q., Gao, R., Wu, W. ... Cao, L. (2015). Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation. International Journal of Oncology, 46, 1317-1327. https://doi.org/10.3892/ijo.2015.2835
MLA
Wang, P., Ma, D., Wang, J., Fang, Q., Gao, R., Wu, W., Lu, T., Cao, L."Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation". International Journal of Oncology 46.3 (2015): 1317-1327.
Chicago
Wang, P., Ma, D., Wang, J., Fang, Q., Gao, R., Wu, W., Lu, T., Cao, L."Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation". International Journal of Oncology 46, no. 3 (2015): 1317-1327. https://doi.org/10.3892/ijo.2015.2835
Copy and paste a formatted citation
x
Spandidos Publications style
Wang P, Ma D, Wang J, Fang Q, Gao R, Wu W, Lu T and Cao L: Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation. Int J Oncol 46: 1317-1327, 2015.
APA
Wang, P., Ma, D., Wang, J., Fang, Q., Gao, R., Wu, W. ... Cao, L. (2015). Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation. International Journal of Oncology, 46, 1317-1327. https://doi.org/10.3892/ijo.2015.2835
MLA
Wang, P., Ma, D., Wang, J., Fang, Q., Gao, R., Wu, W., Lu, T., Cao, L."Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation". International Journal of Oncology 46.3 (2015): 1317-1327.
Chicago
Wang, P., Ma, D., Wang, J., Fang, Q., Gao, R., Wu, W., Lu, T., Cao, L."Silencing HO-1 sensitizes SKM-1 cells to apoptosis induced by low concentration 5-azacytidine through enhancing p16 demethylation". International Journal of Oncology 46, no. 3 (2015): 1317-1327. https://doi.org/10.3892/ijo.2015.2835
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