Plasmodium yoelii infection inhibits colon cancer in mice via modulation of hypoxia-inducible factor-1α expression.

Malignant tumors continue to pose a significant threat to human health, highlighting the need for innovative therapeutic approaches. This study aims to investigate the effects of Plasmodium yoelii (P. yoelii) infection on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA), Von Hippel-Lindau (VHL), and p53 in tumor tissues of colon cancer-bearing mice, as well as their relationship with tumor development, thereby elucidating the antitumor mechanisms associated with Plasmodium infection. To establish a subcutaneous tumor-bearing animal model of colon cancer, CT26.WT colon cancer cells were inoculated subcutaneously into BALB/c mice. The mice were divided into the tumor control group (CT26.WT) and P. yoelii-infected group (CT26.WT + P. yoelii). The experimental group CT26.WT + P. yoelii was infected with 0.2 mL (5 × 10/mL) of P. yoelii-infected red blood cells via intraperitoneal injection. Tumor tissues were collected on the 6th, 12th, and 18th days of P. yoelii infection (tumor-bearing day 12, 18, and 24). RT-qPCR and Western blot analyses were employed to assess the mRNA and protein expression levels of HIF-1α, VHL, VEGFA, and p53 in the tumor tissues. Concurrently, tumor growth was monitored in both the groups, on the 18th day post-inoculation with P. yoelii (tumor-bearing day 24), the P. yoelii-infected group exhibited significantly downregulated expression levels of HIF-1α (P < 0.01) and VEGFA (P < 0.01) in the tumor tissue compared to the tumor control group, while the expression levels of VHL (P < 0.01) and p53 (P < 0.01) were markedly upregulated. By day 21 of tumor inoculation (16th day of P. yoelii infection), tumors in the P. yoelii-infected group ceased to grow and began to shrink significantly, indicating a remarkable inhibitory effect of P. yoelii infection on tumor growth (P < 0.001). Overall, P. yoelii infection effectively inhibits tumor development in tumor-bearing mice by downregulating the expression levels of HIF-1α and VEGFA while upregulating the expression levels of VHL and p53.