Z-VRPR-FMK can inhibit the growth and invasiveness of diffuse large B-cell lymphoma by depressing NF-κB activation and MMP expression induced by MALT1

This study aimed to investigate the therapeutic effect of the mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) on diffuse large B-cell lymphoma (DLBCL) and its underlying molecular mechanism through the application of Z-Val-Arg-Pro-DL-Arg-fluoromethyl ketone (Z-VRPR-FMK). Cultured OCI-LY10 cells and their xenografts in nude mice were treated with Z-VRPR-FMK. The growth and invasiveness of the tumor were observed. The components of the NF-κB signaling pathways, such as P65, MALT1, A20, matrix metalloproteinase 2 (MMP2) and MMP9, were detected using a real-time fluorescent quantitative polymerase chain reaction, immunohistochemical staining, and a Western blot analysis. Z-VRPR-FMK inhibited the growth and invasiveness of OCI-LY10 cells and their xenografts. The increase in the tumor volume was slower in the experimental group than it was in the control group, and the weight of the nude mice was significantly different between the two groups on the 11th and 13th days of treatment. The expression of P65 was significantly lower at the gene level in cultured OCI-LY10 cells and transplanted tumors than in the controls after treatment with Z-VRPR-FMK. The nuclear expression of the P65 protein of xenografts also decreased, but the nuclear expression of the A20 protein followed a reverse pattern. The expressions of the MALT1, MMP2, and MMP9 proteins were lower in the OCI-LY10 cells and transplanted tumors treated with Z-VRPR-FMK compared with the controls. This study indicates that MALT1 might serve as an effective therapeutic target for activated B-cell (ABC)-like DLBCL. Z-VRPR-FMK inhibits the growth and invasiveness of ABC-like DLBCL by depressing the proteolysis of A20, the activation of NF-κB, and the expression of MMP9 and MMP2 induced by the MALT1 protein.

A20; MALT1; MMPs; NFκB; Z-VRPR-FMK; lymphoma.