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.

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.

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