Endoplasmic Reticulum Stress-Mediated Signaling Pathway of Gastric Cancer Apoptosis

Background/Aims: To investigate ER stress-mediated CHOP-signaling pathway of gastric cancer apoptosis in vitro and in vivo. Methodology: Based on the dose-and time-response experiments about tunicamycin (TM), gastric cancer cell line BGC823 was treated with 10 mu g/mL of TM for 24h. BGC823 apoptosis was detected with TUNEL assay and ultrastructural changes in BGC823 cells under ER stress were observed with transmission electron microscopy (TEM). RT-PCR and western blotting were used to determine the expression of ERS-related proteins, glucose-regulated protein 78 (GRP78) and CHOP and apoptosis-associated protein B-cell lymphoma 2 (Bcl-2). After the knockdown of CHOP, the changes were also observed in vitro and in vivo. Results: TEM assay showed that after treatment with TM, BGC823 cell size became smaller with ER dilation, vacuolization and karyopyknosis. RT-PCR and western blotting indicated that TM up-regulated GRP78 and CHOP expression and down-regulated Bcl-2 expression. The knockdown of CHOP could convert Bcl-2 expression and reduce BGC823 apoptosis caused by ERS in vitro and in vivo, but failed to influence GRP78. Conclusions: TM can induce ESR and regulate downstream molecules CHOP up-regulation and Bcl-2 down-regulation which lead to BGC823 apoptosis. This study may provide a new theoretical basis for the pathogenesis of gastric cancer.