Dexmedetomidine promotes autophagy and apoptosis of colon cancer cells by activating endoplasmic reticulum (ER) stress-mediated PERK/eIF2α/ATF4 signaling pathway

BackgroundColon cancer is a malignancy from digestive tract and remains the third most common cancer worldwide. Dexmedetomidine (DEX) can be used for postoperative analgesia in patients with colon cancer and also has biological activities such as anti-oxidative stress, anti-inflammation, and anti-cancer.ObjectiveThis study was designed to explore the functions and mechanism of DEX in regulating colon cancer cell proliferation, apoptosis, and autophagy.ResultsDex reduced LoVo and HCT116 cell viability in a time- and dose-dependent way. Additionally, DEX suppressed colon cancer cell proliferation while promoting cell apoptosis and autophagy. Moreover, chloroquine (a compound used for inhibition of autophagy) reversed the promoting effect of DEX on colon cancer cell apoptosis. Furthermore, DEX activated the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2 alpha)/activating transcription factor 4 (ATF4) signaling pathway. PERK silencing inhibited DEX-induced cell apoptosis and autophagy.ConclusionThis work revealed the anti-cancer effect of DEX treatment by inhibiting colon cancer cell proliferation while promoting cancer cell apoptosis and autophagy via the PERK/eIF2 alpha/ATF4 pathway.