# Molecular Hydrogen Inhibits Colorectal Cancer Growth via the AKT/SCD1 Signaling Pathway.
> AKT/SCD1シグナル経路を介した分子状水素による大腸がん増殖抑制効果の検討


## Abstract

This study examined the anti-tumor properties of molecular hydrogen (H2) in colorectal cancer (CRC) using three cell lines—RKO, SW480, and HCT116. CCK-8, colony formation, and flow cytometry assays revealed that H2 reduced cell proliferation independently of apoptosis, with dose-dependent variation across cell lines. In xenograft mouse models receiving 67% H2 inhalation for two hours daily, both tumor volume and weight were significantly diminished. Western blot and immunohistochemical analyses indicated that H2 lowered phosphorylated AKT (pAKT) and SCD1 protein levels; reintroduction of AKT activity via the activator SC79 reversed the antiproliferative effect. Immunohistochemical evaluation of 491 CRC tissue specimens showed SCD1 overexpression in 70.3% of tumor samples versus 29.7% in normal epithelium, with significant associations to advanced TNM stage, lymph node metastasis, and absence of family CRC history. These findings identify the pAKT/SCD1 axis as a mechanistic target underlying H2-mediated suppression of CRC growth.

### Mechanism

H2 reduces phosphorylated AKT levels, which in turn suppresses the downstream lipid desaturase SCD1, thereby inhibiting CRC cell proliferation. Reactivation of AKT with the agonist SC79 rescues proliferation, confirming the pAKT/SCD1 axis as the operative pathway.

## Bibliographic

- **Authors**: Zhang XQ, Tao G, Zhao Y, Xing S, Jiang J, Liu B, et al.
- **Journal**: Biomed Res Int
- **Year**: 2022
- **PMID**: [35528164](https://pubmed.ncbi.nlm.nih.gov/35528164/)
- **DOI**: [10.1155/2022/8024452](https://doi.org/10.1155/2022/8024452)
- **PMC**: [PMC9071919](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071919/)
- **Study type**: in vitro study
- **Delivery route**: mixed routes
- **Effect reported**: positive
- **H2 concentration**: 67%

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 35528164. https://h2-papers.org/en/papers/35528164
> **Source**: PubMed PMID [35528164](https://pubmed.ncbi.nlm.nih.gov/35528164/)