Overexpression of heme oxygenase-1 induced by constitutively activated NF-κB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma

  • Authors:
    • Jun Huang
    • Pengxiang Guo
    • Dan Ma
    • Xiaojing Lin
    • Qin Fang
    • Jishi Wang
  • View Affiliations

  • Published online on: May 17, 2016     https://doi.org/10.3892/ijo.2016.3529
  • Pages: 253-264
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

There is an urgent requirement for a new therapeutic target for activated B-cell-like lymphoma (ABC-DLBCL), which is known to have dismal outcome and constitutive activation of NF-κB. Heme oxygenase-1 (HO-1) can inhibit apoptosis and promote proliferation in many cancers. To our knowledge, no studies have been performed on the correlation between HO-1 and DLBCL. In this study, immunohistochemical analysis of 31 tumor tissues from DLBCL patients [20 of ABC subtype and 11 of germinal center B-cell-like (GCB) subtype] and 11 normal lymph nodes revealed that HO-1 overexpression was characteristic of ABC-DLBCL. In addition, HO-1 mRNA expression levels were consistent with the immunohistochemistry results. High levels of HO-1 expression were significantly correlated with the involvement of more than 1 extranodal site (p=0.025), with a high positivity rate of Ki-67 (p<0.01). Similar to its anti-apoptotic role in other malignancies, HO-1 upregulation suppressed apoptosis of the ABC-DLBCL cell line OCI-ly10, whereas its downregulation sensitized the tumor cells to chemotherapeutic drugs. Further study demonstrated that the HO-1 overexpression was mediated by constitutively activated NF-κB which together played an anti-apoptotic role in ABC-DLBCL. Combination of the NF-κB inhibitor Bay11‑7082 and the lentivirus vector Lenti-siHO-1 significantly decreased HO-1 protein expression and increased apoptosis in OCI-ly10 cells. However, in GCB-DLBCL cells with low levels of NF-κB expression, the TNF-α-mediated activation of NF-κB leading to HO-1 upregulation rescued the cells from apoptosis caused by HO-1 silencing. These results indicated that HO-1 can be a potential target for the treatment of ABC-DLBCL.
View Figures
View References

Related Articles

Journal Cover

July-2016
Volume 49 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Huang J, Guo P, Ma D, Lin X, Fang Q and Wang J: Overexpression of heme oxygenase-1 induced by constitutively activated NF-κB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma. Int J Oncol 49: 253-264, 2016
APA
Huang, J., Guo, P., Ma, D., Lin, X., Fang, Q., & Wang, J. (2016). Overexpression of heme oxygenase-1 induced by constitutively activated NF-κB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma. International Journal of Oncology, 49, 253-264. https://doi.org/10.3892/ijo.2016.3529
MLA
Huang, J., Guo, P., Ma, D., Lin, X., Fang, Q., Wang, J."Overexpression of heme oxygenase-1 induced by constitutively activated NF-κB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma". International Journal of Oncology 49.1 (2016): 253-264.
Chicago
Huang, J., Guo, P., Ma, D., Lin, X., Fang, Q., Wang, J."Overexpression of heme oxygenase-1 induced by constitutively activated NF-κB as a potential therapeutic target for activated B-cell-like diffuse large B-cell lymphoma". International Journal of Oncology 49, no. 1 (2016): 253-264. https://doi.org/10.3892/ijo.2016.3529