Huang J.,Guiyang Medical University |
Huang J.,Guizhou University |
Huang J.,Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center |
Guo P.,Peoples Hospital of Guizhou Province |
And 9 more authors.
International Journal of Oncology | Year: 2016
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-B. 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-B which together played an anti-apoptotic role in ABC-DLBCL. Combination of the NF-B 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-B expression, the TNF-mediated activation of NF-B 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.
Lin X.,Guiyang Medical College |
Lin X.,The Affiliated Hospital of Guiyang Medical College |
Lin X.,Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center |
Fang Q.,The Affiliated Baiyun Hospital of Guiyang Medical College |
And 19 more authors.
Leukemia Research | Year: 2015
There are few studies on the correlation between heme oxygenase-1 (HO-1) and acute myeloid leukemia (AML). We found that HO-1 was aberrantly overexpressed in the majority of AML patients, especially in patients with acute monocytic leukemia (M5) and leukocytosis, and inhibited the apoptosis of HL-60 and U937 cells. Moreover, silencing HO-1 prolonged the survival of xenograft mouse models. Further studies demonstrated that HO-1 suppressed the apoptosis of AML cells through activating the JNK/c-JUN signaling pathway. These data indicate a molecular role of HO-1 in inhibiting cell apoptosis, allowing it to be a potential target for treating AML. © 2015 Elsevier Ltd.