Erianin reverses 5-FU resistance by targeting CALM1/CAMKK2 and activating autophagy in colorectal cancer
- Chem Biol Interact. 2025 Sep 19:421:111750. doi: 10.1016/j.cbi.2025.111750.
- 1. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 2. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 3. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 4. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 5. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 6. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 7. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 8. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
- 9. Department of Clinical Nutrition, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: [email protected].
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 subsequently increasing the phosphorylation levels of CAMKK2. This interaction facilitates Autophagy in 5-FU-resistant CRC cells, ultimately leading to tumor cell death.
Conclusion: Erianin sensitized the resistant CRC cells to 5-FU by activating the CALM1/CAMKK2 signaling pathway, thereby inducing Autophagy. The combination of 5-FU and Erianin presents a promising therapeutic approach to enhance survival outcomes in patients with refractory CRC.
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Cat. No.Product NameDescriptionTargetResearch Area
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Research Areas: Cancer
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Research Areas: Cancer
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Research Areas: Cancer
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Research Areas: Metabolic Disease