Erianin reverses 5-FU resistance by targeting CALM1/CAMKK2 and activating autophagy in colorectal cancer

作者：Fangyuan Zhou, Luorui Shang, Jinxiao Li, Mengqi Zhang, Shuhan Wang, Yuju Cai, Qifeng Lin, Haiyang Gao, Shenglan Yang · 发表于：Chemico-Biological Interactions · 年份：2025 · DOI：10.1016/j.cbi.2025.111750 · 被引用次数：2 · 研究领域：Autophagy in Disease and Therapy、Berberine and alkaloids research、Biological and pharmacological studies of plants

BACKGROUND: Chemoresistance represents a significant factor contributing to the failure of clinical treatments in colorectal cancer (CRC), with resistance to 5-fluorouracil (5-FU) being notably prevalent. Erianin has demonstrated potential in reversing tumor resistance; however, its specific effects and underlying mechanisms in the context of 5-FU-resistant CRC require comprehensive validation. METHODS: The half-maximal inhibitory concentration (IC50) of Erianin and 5-FU was determined using the CCK8 assay. CRC cells resistant to 5-FU were induced by progressively increasing concentrations of 5-FU. Cellular proliferation, migration, and invasion were evaluated via 5-ethynyl-2'-deoxyuridine (EdU) assays, wound-healing assays, and Transwell Matrigel invasion assays. The expression levels of protein and mRNA expression levels for various molecules were quantified using Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). Immunofluorescence assays were employed to assess the expression of autophagy-related markers. The in vivo therapeutic efficacy of Erianin was assessed using a xenograft tumor model. RESULTS: Erianin effectively reinstated the sensitivity of 5-FU-resistant CRC cells to 5-FU, significantly reducing tumor cell proliferation, migration, and invasion, as well as inhibiting xenograft tumor growth. Mechanistic investigations demonstrated that Erianin targets and binds to the calmodulin 1 (CALM1) protein, enhancing its stability and sub...