The role of dinutuximab beta with beta cell function, apoptosis, and proliferation: new approaches to proteomic analysis of insulinoma.

Abstract

The aim of this study was to investigate gene expressions related to beta cell function, and the altered protein profiles in insulinoma INS-1 cells following DB application, under both cytotoxic and non-cytotoxic conditions, with a focus on cell death and proliferation. Caspase 3 activity, LDH level, Bax, Bcl-2, PCNA, MafA, Nkx6.1, Pdx1, NeuroD1, and Pax6 gene expressions, TOS, TAS, and OSI were demonstrated. Protein profiles were analyzed using LC-MS/MS. The upstream and downstream proteins using the IPA database were determined. ERP29, UBE2V2, UBE2L6, PSMA4, TSMB10, ARF1, NUDCD2, ARF3, IRS1, PTEN, AKT, HSPA8, and Fibronectin levels were shown. The changes were observed in genes depending on pancreatic beta cell function and apoptosis. Bcl2, MafA, Nkx6.1, Pdx1, and NeuroD1 gene levels decreased, while Bax and Pax6 gene levels and TAS and TOS levels increased in the group given STZ + DB. PCNA, Bcl-2, Nkx6.1, Pdx1, and Pax6 gene levels increased, while MafA gene levels decreased in the group given DB. The protein ubiquitination pathway more predominates than the other many signaling pathways. Several proteins not previously associated, or only indirectly linked, with beta cell function, apoptosis, or proliferation were identified and characterized for the first time in insulinoma. These findings provide new insights and potential targets for the treatment of pancreatic cancer.