<em>Plasmodium </em>infection downregulates hypoxia‑inducible factor 1&alpha; expression to suppress the vascularization and tumorigenesis of liver cancer

Wu,Runling; Chen,Xiao; Chen,Huan; Li,Mei; Liang,Yun

doi:10.3892/ol.2024.14737

Plasmodium infection downregulates hypoxia‑inducible factor 1α expression to suppress the vascularization and tumorigenesis of liver cancer

Authors:
- Runling Wu
- Xiao Chen
- Huan Chen
- Mei Li
- Yun Liang
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Affiliations: Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Clinical Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: October 14, 2024 https://doi.org/10.3892/ol.2024.14737
Article Number: 604
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is characterized by hypervascularization. Anti‑angiogenic agents may normalize the tumor vasculature and improve the efficacy of other treatments. The present study aims to investigate the anti‑angiogenic effect of Plasmodium infection in a mouse model of implanted liver cancer cells. HepG2 cells were injected into the left liver lobe of nude mice as a model of in situ hepatic tumorigenesis. Plasmodium yoelii parasitized erythrocytes were administered in the animal model of liver cancer to introduce Plasmodium infection. The tumor growth and microvascular density were determined in the presence or absence of Plasmodium infection. The expression levels of hypoxia‑inducible factor 1α (HIF‑1α) and angiogenesis‑related factors were evaluated using western blotting and reverse transcription‑quantitative PCR analysis. The results demonstrated that Plasmodium infection suppressed tumor growth and vascularization in the mouse model of implanted HepG2 cells. Plasmodium parasites reduced the expression of pro‑angiogenic factors (vascular endothelial growth factor A and angiopoietin 2), matrix metalloproteinases [(MMP)2 and MMP9] and inflammatory cytokines [tumor necrosis factor α, interleukin 6 (IL)‑6) and IL‑1β] in both hepatic and tumor tissues. HIF‑1α was downregulated in both hepatic and tumor tissues upon Plasmodium infection, and HIF‑1α overexpression rescued angiogenesis and tumor growth under the condition of Plasmodium infection. In conclusion, the results of the present study demonstrated the anti‑angiogenic and anti‑tumorigenic effects of Plasmodium infection on liver cancer through downregulating HIF‑1α expression, indicating that Plasmodium parasites could be developed as an intervention strategy to restrain neo‑angiogenesis in liver cancer.

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