Esketamine Enhances the Chemosensitivity of Colorectal Adenocarcinoma Cells to 5-Fluorouracil via AMPK/mTOR/HMMR Signaling Pathway.
Oncology research January 1, 2026 Yuerou Feng, Panpan Tong, Shuwen Fu et al.
Combining esketamine with 5-fluorouracil (5-FU) synergistically reduces proliferation, migration, and invasion while increasing apoptosis in colorectal adenocarcinoma cell lines compared to 5-FU alone. Mechanistically, esketamine amplifies 5-FU-driven AMPK phosphorylation, which inhibits both mTOR and HMMR signaling. This activation of the AMPK/mTOR/HMMR axis enhances chemosensitivity, suggesting esketamine could serve as an adjunct to improve 5-FU efficacy and potentially address cancer-related pain and depression.