2. Academic Validation
  3. Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3β/TCF7/MMP9 pathway and synergies with capecitabine

Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3β/TCF7/MMP9 pathway and synergies with capecitabine

  • Cancer Lett. 2023 Dec 13:216596. doi: 10.1016/j.canlet.2023.216596.
Xiaoshuo Dai 1,  Wei Chen 1,  Yan Qiao 2,  Xinhuan Chen 2,  Yihuan Chen 1,  Kai Zhang 1,  Qiushuang Zhang 1,  Xiaoxuan Duan 1,  Xiang Li 2,  Jimin Zhao 2,  Fang Tian 2,  Kangdong Liu 2,  Ziming Dong 2,  Jing Lu 3
Affiliations

Affiliations

  • 1 Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, PR China.
  • 2 Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, PR China; Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan Province, 450001, PR China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, PR China.
  • 3 Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, PR China; Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, Henan Province, 450001, PR China; State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, PR China. Electronic address: lujing@zzu.edu.cn.
PMID: 38101610 DOI: 10.1016/j.canlet.2023.216596
Abstract

Patients with colorectal Cancer (CRC) suffer from poor prognosis and lack effective drugs. Dihydroartemisinin (DHA) has anti-cancer potential but the mechanism remains unclear. We elucidated the effects and mechanism of DHA on CRC development with the aim of providing an effective, low-toxicity drug and a novel strategy for CRC. Herein, proliferation assay, transwell assay, tube formation assay, metastasis models, PDX model and AOM/DSS model were used to reveal the effects of DHA on CRC. The key pathway and target were identified by RNA-seq, ChIP, molecular docking, pull down and dual-luciferase reporter assays. As a result, DHA showed a strong inhibitory effect on the growth, metastasis and angiogenesis of CRC with no obvious toxicity, and the inhibitory effect was similar to that of the clinical drug Capecitabine (Cap). Indeed, DHA directly targeted GSK-3β to inhibit CRC development through the GSK-3β/TCF7/MMP9 pathway. Meaningfully, DHA in combination with Cap enhanced the anti-cancer effect, and alleviated Cap-induced diarrhoea, immunosuppression and inflammation. In conclusion, DHA has the potential to be an effective and low-toxicity drug for the treatment of CRC. Furthermore, DHA in combination with Cap could be a novel therapeutic strategy for CRC with improved efficacy and reduced side effects.

Keywords

Capecitabine; Colorectal cancer; Dihydroartemisinin; GSK-3β.

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