5-Fluorouracil-based chemotherapy disrupts autophagy flux and protein synthesis in cultured myotubes: a role for mTORC1 signaling

Halle JL, Zhang Q, Jenkins T, Carson JA · 2026 · American Journal of Physiology-Cell Physiology · Atlas ID HAL2026

What this study shows

FOLFOX and oxaliplatin disrupted mTORC1/AMPK regulation of autophagy flux and protein synthesis in cultured myotubes; the effect was not easily reversible on drug withdrawal. Rapamycin (but not metformin) restored autophagy flux and AMPK phosphorylation, though without restoring protein synthesis.

Abstract

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5-Fluorouracil-based chemotherapies, such as FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), are used to treat colon cancer but also induce skeletal muscle toxicities. While FOLFOX can disrupt muscle autophagy signaling in vivo, the upstream mechanisms underlying this effect, as well as the roles of mTORC1 and AMPK signaling, require further investigation.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: C2C12 mouse myotubes (in vitro), with and without CT26 colon-tumor-cell-conditioned media) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	C2C12 mouse myotubes (in vitro), with and without CT26 colon-tumor-cell-conditioned media
Journal	American Journal of Physiology-Cell Physiology
Year	2026
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1152/ajpcell.00321.2026 · PMID 42734427

Extracted findings

Intervention	5-FU, 5-FU+leucovorin, oxaliplatin, combined FOLFOX regimen; rescue with rapamycin or metformin
Target	mTORC1/AMPK/ULK1 signaling and autophagy flux
Model	Mouse (C2C12 myotubes, in vitro)
Effect	FOLFOX/oxaliplatin suppressed autophagy flux, AMPK and ULK1(S555) phosphorylation, and protein synthesis; effect persisted after drug withdrawal; rapamycin (not metformin) restored autophagy flux and AMPK phosphorylation without restoring protein synthesis

Cite this paper

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Halle, J. L., Zhang, Q., Jenkins, T., & Carson, J. A. (2026). 5-Fluorouracil-based chemotherapy disrupts autophagy flux and protein synthesis in cultured myotubes: a role for mTORC1 signaling. American Journal of Physiology-Cell Physiology. https://doi.org/10.1152/ajpcell.00321.2026

@article{HAL2026,
  author       = {Halle, J. L. and Zhang, Q. and Jenkins, T. and Carson, J. A.},
  title        = {{5-Fluorouracil-based chemotherapy disrupts autophagy flux and protein synthesis in cultured myotubes: a role for mTORC1 signaling}},
  journal      = {American Journal of Physiology-Cell Physiology},
  year         = {2026},
  doi          = {10.1152/ajpcell.00321.2026},
  note         = {PMID: 42734427},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record HAL2026) [Data set]. https://mtor-atlas.org/study/HAL2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_HAL2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record HAL2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/HAL2026/},
  doi          = {10.5281/zenodo.22059963}
}