# Artemether as a modulator of EMT in colorectal cancer: enhancing radiosensitivity and reversing chemo-radiation resistance

## TL;DR

Artemether enhances the effectiveness of radiotherapy in colorectal cancer by reversing resistance and regulating EMT processes.

## Contribution

Artemether is shown to reverse chemo-radiation resistance and enhance radiosensitivity in colorectal cancer via EMT modulation.

## Key findings

- Artemether combined with radiotherapy suppressed tumor growth and induced cell death in xenograft models.
- Artemether reversed EMT by upregulating E-cadherin and β-Catenin while downregulating N-Cadherin, Vimentin, Snail, Slug, and Twist.
- Artemether significantly enhanced radiosensitivity in chemo-radiation-resistant colorectal cancer cells.

## Abstract

The efficacy of conventional chemoradiotherapy for colorectal cancer is often limited by resistance, with epithelial-mesenchymal transition being a key mechanism. Although the artemisinin derivative artemether (ARE) has shown antitumor potential, it remains unclear whether it can enhance radiosensitivity and reverse chemo-radiation resistance in colorectal cancer by regulating EMT. This study aimed to investigate the radiosensitizing and resistance-reversing effects of ARE on human colorectal cancer xenografts in nude mice and to elucidate the underlying mechanism related to EMT regulation.

A nude mouse xenograft model using human colorectal cancer HCT116 and HCT116-chemo-radiation resistant (HCT116-CRR) cells was established.

ARE combined with radiotherapy suppressed tumor growth in nude mice and induced cell death via necrosis and apoptosis. After ARE combined with radiotherapy, β-Catenin was increased in human colorectal cancer HCT116 cells implanted in nude mice, while Vimentin was decreased. In HCT116-CRR cells transplanted into nude mice, the E-cadherin and β-Catenin were upregulated, whereas N-Cadherin, Vimentin, Snail, Slug, and Twist were downregulated. ARE effectively significantly enhanced radiosensitivity and reversed chemo-radiation resistance by suppressing EMT.

These findings provide both mechanistic insights and experimental validation for the potential application of ARE as a radiosensitizer in colorectal cancer radiotherapy.

The online version contains supplementary material available at 10.1186/s12876-026-04653-4.