Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes microenvironment-mediated imatinib resistance in chronic myeloid leukemia

Liu, Ping; Ma, Dan; Yu, Zhengyu; Zhe, Nana; Ren, Mei; Wang, Ping; Yu, Meisheng; Huang, Jun; Fang, Qin; Wang, Jishi

doi:10.1016/j.biopha.2017.04.076

Cited by 28 publications

(18 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, HO-1 protected BMSCs from ROS through secreting IL-10 in the case of iron overload. 18,33 In this study, HO-1 expression was higher in BMSCs derived from B-ALL patients, especially in those from resistant cases ( Figure 2). Meanwhile, HO-1 overexpression in BMSCs mediated the resistance of B-ALL cells to VCR (Figure 3).…”

Section: Discussionmentioning

confidence: 48%

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Wang

Lü

et al. 2019

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Chemoresistance often causes treatment failure of B‐cell acute lymphoblastic leukemia (B‐ALL). However, the mechanism remains unclear at present. Herein, overexpression of heme oxygenase‐1 (HO‐1) was found in the bone marrow stromal cells (BMSCs) from B‐ALL patients developing resistance to vincristine (VCR), a chemotherapeutic agent. Two B‐ALL cell lines Super B15 and CCRF‐SB were cocultured with BMSCs transfected with lentivirus to regulate the expression of HO‐1. Silencing HO‐1 expression in BMSCs increased the apoptotic rates of B‐ALL cell lines induced by VCR, whereas upregulating HO‐1 expression reduced the rate. Cell cycle can be arrested in the G2/M phase by VCR. In contrast, B‐ALL cells were arrested in the G0/G1 phase due to HO‐1 overexpression in BMSCs, which avoided damage from the G2/M phase. Vascular endothelial growth factor (VEGF) in BMSCs, as a key factor in the microenvironment‐associated chemoresistance, was also positively coexpressed with HO‐1. VEGF secretion was markedly increased in BMSCs with HO‐1 upregulation but decreased in BMSCs with HO‐1 silencing. B‐ALL cell lines became resistant to VCR when cultured with VEGF recombinant protein, so VEGF secretion induced by HO‐1 expression may promote the VCR resistance of B‐ALL cells. As to the molecular mechanism, the PI3K/AKT pathway mediated regulation of VEGF by HO‐1. In conclusion, this study clarifies a mechanism by which B‐ALL is induced to resist VCR through HO‐1 overexpression in BMSCs, and provides a novel strategy for overcoming VCR resistance in clinical practice.

show abstract

Section: Discussionmentioning

confidence: 48%

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Wang

Lü

et al. 2019

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that HIF-1 is associated with tumor metastasis, angiogenesis, and chemotherapy resistance (Masoud and Li, 2015;Schito and Semenza, 2016). It has been reported that HO-1 is also involved in the resistance to chemotherapy agents (Liu et al, 2017). Therefore, to examine the relationship between HO-1 induction and susceptibility of TS-PDT, we next examined the effect of ZnPPIX, one of HO-1 inhibitor (Hirai et al, 2007), on the TS-PDT-induced cytotoxicity in rat malignant meningioma KMY-J cells.…”

Section: Resultsmentioning

confidence: 98%

Photodynamic therapy using talaporfin sodium induces heme oxygenase-1 expression in rat malignant meningioma KMY-J cells

et al. 2018

View full text Add to dashboard Cite

Photodynamic therapy (PDT) using talaporfin sodium (TS) is tumor cell-selective less invasive therapy for the treatment of malignant glioma. We previously demonstrated that PDT using TS (TS-PDT) treatment exhibits anti-tumor activity against not only glioblastoma cells but also malignant meningioma cells. In general, various stress response proteins have been reported to affect the sensitivity determination for anticancer agents against tumor cells. However, the relationship between the therapeutic effect of TS-PDT and stress response systems in tumor cells is not adequately investigated. In this study, we investigated the gene expression of stress response proteins, including Sod1, Cat1, Gstp1, Gpx1, Nqo1, and Hmox1, in rat malignant meningioma KMY-J cells after treatment of TS-PDT. TS-PDT treatment significantly decreased the cell viability when compared with the no laser irradiation group. In morphological observation, TS at 25.6 µM treatment exhibited a significant cytotoxic effect after 12 hr of laser irradiation to KMY-J cells. After 3 and 6 hr of TS-PDT treatment, mRNA expression of heme oxygenase-1 (HO-1, encoded by Hmox1) was significantly increased by TS-PDT treatment. We also demonstrated that zinc protoporphyrin IX (ZnPPIX), a HO-1 inhibitor, significantly augmented the cytotoxic effect of TS-PDT treatment. These data suggest that HO-1 induction may contribute to a protective response against TS-PDT treatment in the malignant meningioma cells and may attenuate the therapeutic effect for TS-PDT treatment.

show abstract

“…It is known that HO-1 expression inhibited apoptosis and HO-1 silencing promoted apoptosis. 33,34 BCLAF1 is a direct downstream of NF-kB, and whether it mediates apoptosis of DLBCL cells via HO-1 requires further exploration in future experiments. In conclusion, BCLAF1 is a potential epigenetic therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism

Cheng

et al. 2018

Cancer Biology & Therapy

Self Cite

View full text Add to dashboard Cite

Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult lymphoma. It is a group of malignant tumors with a large number of clinical manifestations and prognoses. Therefore, it is necessary to explore its unknown potential therapeutic targets. Histone deacetylase inhibitor (HDACi) is a novel drug for the treatment of DLBCL, however pan-HDACis cannot be ignored because of their clinical efficacy. By contrast, specific HDACi is well-tolerated, and LMK-235 is a novel HDACi that is a specific inhibitor of HDAC4 and HDAC5. In this study, we investigated the up-regulation of BCLAF1 through NF-κB signaling pathways in LMK-235, mediating the apoptosis of two diffuse large B-cell lymphoma cell lines, OCI-LY10 and OCI-LY3. Further studies showed that BCLAF1 expression was increased in DLBCL cells after treatment with the NF-κB inhibitor Bay11-7082. The combination of Bay11-7082 and siRNA si-HDAC4 significantly increased BCLAF1 expression and further increased apoptosis. These results indicate that BCLAF1 plays an important role in LMK-235-mediated apoptosis and may be a potential target for the treatment of diffuse large B-cell lymphoma.

show abstract

Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes microenvironment-mediated imatinib resistance in chronic myeloid leukemia

Cited by 28 publications

References 31 publications

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Overexpression of heme oxygenase‐1 in microenvironment mediates vincristine resistance of B‐cell acute lymphoblastic leukemia by promoting vascular endothelial growth factor secretion

Photodynamic therapy using talaporfin sodium induces heme oxygenase-1 expression in rat malignant meningioma KMY-J cells

Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism

Contact Info

Product

Resources

About