[SOD1 Inhibitor LCS-1 Induces Apoptosis in Diffuse Large B-Cell Lymphoma Cells].

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.