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[SOD1 Inhibitor LCS-1 Induces Apoptosis in Diffuse Large B-Cell Lymphoma Cells]
Wei-Cheng Zheng1,2, Wen-Yu Shi1
1Department of Oncology, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
Objective:
To investigate the expression of superoxide dismutase 1 (SOD1) in tumor tissue of patients with diffuse large B-cell lymphoma (DLBCL) and in DLBCL cell lines, to explore the effect of SOD1 inhibitor LCS-1 on proliferation and apoptosis of DLBCL cell lines and analyze its possible mechanisms of action.
Methods:
Immunohistochemistry assay was used to detect the expression level of SOD1 in DLBCL tissues and reactive lymph node hyperplasia tissues. The expression levels of SOD1 protein in DLBCL cell lines (TMD-8, OCI-Ly10, OCI-Ly18, OCI-Ly19) were detected by Western blot. After the DLBCL cell lines were treated with different concentrations of LCS-1, the cell proliferation activity was detected by CCK-8 assay, the expression levels of SOD1 protein was detected by Western blot, and the cell apoptosis was detected by TUNEL method. The genes enrichment of the SOD1 high expression group were analyzed by the KEGG database.
Results:
The expression levels of SOD1 in the tumor tissues of DLBCL patients and DLBCL cell lines TMD-8, OCI-Ly18, and OCI-Ly19 were significantly increased. SOD1 inhibitor LCS-1 showed a certain inhibitory effect on the activity of DLBCL cell lines TMD-8, OCI-Ly18, and OCI-Ly19 in a concentration- and time-dependent manner (r =0.730, r =0.929,r =0.976). After being treated with different concentrations of LCS-1, the expression level of SOD1 protein in OCI-Ly18 and OCI-Ly19 cell lines decreased in a concentration-dependent manner (r =0.860, r =0.970); LCS-1 significantly promoted the apoptosis of DLBCL cell lines OCI-Ly18 and OCI-Ly19 at a concentration of 3 μmol/L (P < 0.001). KEGG enrichment analysis suggested that SOD1 may play an important role through oxidative phosphorylation (P =0.002, FDR=0.003) and ribosome (P =0.004, FDR=0.005) pathways in DLBCL.
Conclusion:
The expression levels of SOD1 in tumor tissues of DLBCL patients were significantly increased. As a SOD1 inhibitor, LCS-1 can significantly inhibit the viability and proliferation of DLBCL cell lines OCI-Ly18 and OCI-Ly19, and promote cell apoptosis, which provides a new idea for the treatment of DLBCL.
Insights
Superoxide dismutase 1 (SOD1) is elevated in diffuse large B-cell lymphoma (DLBCL). The SOD1 inhibitor LCS-1 effectively reduces DLBCL cell viability and proliferation while promoting apoptosis, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Context:
- Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma.
- Understanding the molecular mechanisms driving DLBCL proliferation is crucial for developing targeted therapies.
- Superoxide dismutase 1 (SOD1) is implicated in cellular defense against oxidative stress and has been linked to various cancers.
Purpose:
- To investigate the expression of SOD1 in DLBCL tumor tissues and cell lines.
- To evaluate the therapeutic potential of the SOD1 inhibitor LCS-1 on DLBCL cell proliferation and apoptosis.
- To elucidate the underlying mechanisms of LCS-1 action in DLBCL.
Summary:
- Immunohistochemistry and Western blot analyses revealed significantly increased SOD1 expression in DLBCL tissues and cell lines compared to controls.
- Treatment with LCS-1 demonstrated a dose- and time-dependent inhibition of DLBCL cell viability and proliferation.
- LCS-1 treatment also significantly promoted apoptosis in DLBCL cell lines and reduced SOD1 protein levels, with KEGG analysis suggesting involvement of oxidative phosphorylation and ribosome pathways.
Impact:
- This study identifies SOD1 as a potential therapeutic target in DLBCL.
- LCS-1 shows promise as a novel agent for inhibiting DLBCL progression.
- The findings provide a basis for further preclinical and clinical investigations of SOD1-targeted therapies for DLBCL.
