Abstract
Objective:Cellular senescence has been thought to be an important barrier to tumor formation. Recent studies have shown that stress-induced premature senescence (SIPS) can promote partial tumor invasion, but how SIPS affects diffuse large B-cell lymphoma (DLBCL) remains inconclusive. This study aimed to address that issue.Materials and Methods:The immunophenotype of the LY8 cell line was measured with flow cytometry. SIPS induced by tert-butyl hydroperoxide (tBHP) was detected by senescence β-galactosidase staining. Cell proliferation was analyzed with CCK8 and expression levels of ARHGAP18 (SENEX gene-encoding protein), p16/p21, and Rb/pRb were measured with western blot. LY8 cells were transfected with SENEX-SiRNA/NC and verified by western blot.Results:Our results suggested that the immunophenotype of the LY8 cell line is CD19-, CD20-, and CD10-positive and the immunoglobulin light chain is the kappa type. The cellular senescence model of DLBCL could be successfully induced by 30 μM tBHP. ARHGAP18, p21, p16, and Rb protein levels were significantly increased but the level of pRb expression was decreased in the SIPS group compared with other groups. Meanwhile, the proliferation rate was increased in the SIPS group more than other tBHP groups. Furthermore, the expressions of p21 and p16 were significantly decreased in the SENEX-SiRNA group compared with the negative control group.Conclusion:SIPS formation activates ARHGAP18 and the p16/Rb pathway and promotes DLBCL cell proliferation. Furthermore, SENEX activates the p16 pathway in DLBCL. SIPS promotes proliferation by activating SENEX and the p16/Rb pathway in DLBCL. SENEX-related SIPS may serve as an important target for relapsed/refractory DLBCL therapy.
Highlights
Diffuse large B-cell lymphoma (DLBCL), representing about 30%-40% of non-Hodgkin’s lymphoma (NHL), is the most common subtype [1]
ARHGAP18, p21, p16, and Rb protein levels were significantly increased but the level of pRb expression was decreased in the stress-induced premature senescence (SIPS) group compared with other groups
SENEX-related SIPS may serve as an important target for relapsed/refractory DLBCL therapy
Summary
Diffuse large B-cell lymphoma (DLBCL), representing about 30%-40% of non-Hodgkin’s lymphoma (NHL), is the most common subtype [1]. Studies have suggested that this difference may be related to the specific immune escape protection mechanism of DLBCL [5]. Tumor cell immune escape is associated with the paracrine effects of cellular senescence [6,7,8]. Cellular senescence refers to a relatively stable and continuous state leading to cell detachment from the cell cycle and loss of proliferation during various non-lethal pressures from inside and outside. It is divided into replicative senescence and stress-induced premature senescence (SIPS) according to the different mechanisms [9]. Recent studies have shown that SIPS can promote partial tumor invasion [11]
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