Oral cancer cells affect pancreatic β-cell function through transmissible endoplasmic reticulum stress.

OBJECTIVES:In this study, we aimed to investigate whether oral cancer cells affect pancreatic β-cells function through transmissible endoplasmic reticulum stress (TERS). METHODS:Tunicamycin (TM) was selected as the endoplasmic reticulum stress (ERS) inducer. The human oral cancer cell lines CAl-27 and SCC-25 were selected as the donor cells, and mouse insulinoma 6 (MIN6) cell lines were chosen as the recipient cells. Quantitative real-time polymerase chain reaction (qPCR) and Western blot (WB) analysis were used to detect ERS markers and insulin expression. The TdT-mediated dUTP nick-end labeling (TUNEL) method was applied to detect apoptosis levels. The clone formation method was utilized to detect cell proliferation capability. The secretory function of pancreatic β-cells was detected with an enzyme linked immunosorbent assay (ELISA) kit and a bicinchoninic acid (BCA) kit. RESULTS:The MIN6 cells were subjected to TM stimulation. qPCR and WB analysis revealed that ERS markers were upregulated. This result implied that the MIN6 cells can induce ERS. The supernatant of oral cancer cells under ERS was added to the MIN6 cells. qPCR and WB analysis showed that the oral cancer cells that had been subjected to ERS could induce ERS in the MIN6 cells, that is, the phenomenon of TERS occurred. The TUNEL assay indicated that the apoptosis of the MIN6 cells increased under TERS. The clone formation assay demonstrated that the proliferation capability of the MIN6 cells decreased under TERS. qPCR and WB analysis revealed that under TERS, insulin synthesis by the MIN6 cells decreased and insulin synthesis was inhibited at the translation level. The ELISA and BCA kits demonstrated that insulin secretion by the MIN6 cells was reduced under TERS. CONCLUSIONS:Oral cancer cells can affect pancreatic β-cells through TERS, resulting in increased apoptosis, decreased viability, and reduced insulin secretion and synthesis capability.