Imatinib ‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress.

Imatinib‑induced apoptosis of gastric cancer cells is mediated by endoplasmic reticulum stress. Oncol Rep. 2018 Dec 19;: Authors: Kim JL, Lee DH, Jeong S, Kim BR, Na YJ, Park SH, Jo MJ, Jeong YA, Oh SC Abstract Imatinib is a powerful tyrosine kinase inhibitor that specifically targets BCR‑ABL, c‑KIT, and PDGFR kinases, and is used in the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, and other types of cancers. However, the possible anticancer effects of imatinib in gastric cancer have not yet been explored. The present study evaluated the in vitro effects of imatinib on gastric cancer cells and determined the molecular mechanism underlying these effects. We determined that imatinib induced mitochondria‑mediated apoptosis of gastric cancer cells by involving endoplasmic reticulum (ER) stress‑associated activation of c‑Jun NH2‑terminal kinase (JNK). We also found that imatinib suppressed cell proliferation in a time‑ and dose‑dependent manner. Cell cycle analysis revealed that imatinib‑treated AGS cells were arrested in the G2/M phase of the cell cycle. Moreover, imatinib‑treated cells exhibited increased levels of phosphorylated JNK, and of the transcription factor C/EBP homologous protein, an ER stress‑associated apoptotic molecule. Results of cell viability assays revealed that treatment with a combination of imatinib and chemotherapy agents irinotecan or 5‑Fu synergistical...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research