Hypofractionated radiotherapy (RT) combined with dihydroartemisinin (DHA): No synergistic effect observed in a preliminary animal study

Abstract

Purpose: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Dihydroartemisinin (DHA) is an anti-malaria agent and recent evidence indicates a broad anti-cancer activity. Radiotherapy (RT) is the cornerstone of cancer treatment and often has synergistic effects when combined with chemotherapy or targeted therapy. We aim to investigate whether synergistic effect exists for RT combined with DHA in a preliminary animal study of CRC treatment.

Methods: Twenty-four BALB/c nude mice were subcutaneously injected with 5.0 × 10⁶ cells of the murine CRC cell line CT26. When tumor xenografts were formed (∼ 100 mm³), mice were randomly allocated into four groups (n = 6 per group) and the tumor-bearing mice were intra-abdominally injected at Day 7, 9, 11 with PBS (control), 6Gy irradiation (RT), DHA (50mg/Kg), and DHA with irradiation (DHA+RT). All RT was performed on a medical linear accelerator using collimated anterior posterior 6MV photon beam conformal to tumor xenografts. The tumor volume was measured using an electronic caliper and was calculated based on the length (L) and the width of the tumor using the formula V = (L x W²)/2. Tumor weight was also measured after mice sacrificed. Histological assay was conducted, including using gammaH2AX for DNA double strand breaks (DSB) analysis.

Results: The tumor weight was 2.4±0.8g, 2.5±0.6g, 0.4±0.2g, and 0.4±0.1g for the control, DHA, RT, and DHA+RT groups, respectively. Significant difference was observed between the control and RT groups, and between the control and DHA+RT groups (p<0.05). However, there was almost no difference between the RT alone and DHA+RT groups. The longitudinal change in tumor volume showed tumor progression inhibition in the RT and DHA+RT groups, but not so obvious in the DHA group, which was consistent with histological assay.

Conclusion: Similar treatment efficacy is observed in the RT alone and concurrent DHA+RT group. No significant difference in tumor volume or weight or tumor progression inhibition is observed between the RT alone and concurrent DHA+RT groups, demonstrating that DHA might not provide synergistic effect with RT for the proposed hypofractionated radiation dose regimen.

Keywords

colorectal cancer / Dihydroartemisinin / radiotherapy / synergy

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2025 The Author(s). Precision Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Shandong Cancer Hospital & Institute.