Tumor necrosis factor receptor 2 may promote the proliferation and drug resistance of Kapras299 and L428 lymphoma cells via the AKT and WNT/β-catenin signaling pathways.

Circulating soluble tumor necrosis factor receptor 2 (sTNFR2) has been associated with a relatively poor prognosis in various types of lymphoma. However, the specific role of TNFR2 expression in lymphoma cells remains uncharacterized. In the present study, TNFR2 expression was quantified in the Hodgkin lymphoma cell line, L428, and the anaplastic large-cell lymphoma cell line, Karpas299, using RT-PCR and western blot analyses. Karpas299 cells exhibited higher TNFR2 expression than L428 cells. Proliferation and drug resistance experiments demonstrated that Karpas299 cells also possessed a greater proliferative ability and resistance to adriamycin (ADM) than L428 cells, with 50% inhibitory concentrations (IC) of 1.423±0.24 µmol/l for Karpas299 cells, compared with 0.728±0.15 µmol/l for L428 cells (P<0.05). The knockdown of TNFR2 in Karpas299 cells significantly reduced their proliferative ability; when treated with ADM, the cell inhibition rate increased from 49.34±5.42% to 74.13±6.81% (P<0.05). The upregulation of TNFR2 in L428 cells significantly increased their proliferative ability; when treated with ADM, the cell inhibition rate decreased from 47.03±5.25% to 28.71±4.90% (P<0.05). Investigation of the underlying molecular mechanism indicated that the upregulation of TNFR2 expression in L428 cells increased the expression of β-catenin and the phosphorylation of AKT. In L428 cells overexpressing TNFR2, the β-catenin blocker, DKK1, or the AKT inhibitor, LY294002, abrogated the increase in proliferation induced by TNFR2 and increased cell inhibition rate upon treatment with ADM. In summary, the present study demonstrated that TNFR2 promoted the proliferative and drug resistance abilities of lymphoma cells via the AKT and WNT/β-catenin signaling pathways. This may provide the experimental basis for the further study of TNFR2 activity in lymphoma cells and warrant its investigation as a therapeutic target for lymphoma.