2. Academic Validation
  3. Plasmodium infection prevents recurrence and metastasis of hepatocellular carcinoma possibly via inhibition of the epithelial‑mesenchymal transition

Plasmodium infection prevents recurrence and metastasis of hepatocellular carcinoma possibly via inhibition of the epithelial‑mesenchymal transition

  • Mol Med Rep. 2021 Jun;23(6):418. doi: 10.3892/mmr.2021.12057.
Yun Liang # 1,  Xiao Chen # 2,  Zhu Tao 3,  Meng Ma 2,  Dickson Adah 2,  Xiaofen Li 2,  Lingling Dai 2,  Wenting Ding 3,  Songwe Fanuel 2,  Siting Zhao 2,  Li Qin 3,  Xiaoping Chen 2,  Xiaowen Zhang 4
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
  • 2 State Key Laboratory of Respiratory Disease, Center of Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China.
  • 3 CAS‑Lamvac Biotech Co., Ltd., Guangzhou, Guangdong 510670, P.R. China.
  • 4 Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China.
  • # Contributed equally.
PMID: 33846776 DOI: 10.3892/mmr.2021.12057
Abstract

Postoperative recurrence causes a high mortality rate among patients with hepatocellular carcinoma (HCC). The current study aimed to determine the effects of Plasmodium Infection on HCC metastasis and recurrence. The antitumor effects of Plasmodium Infection were determined using two murine orthotopic HCC models: The non‑resection model and the resection model. Tumour tissues derived from tumour‑bearing mice treated with or without Plasmodium Infection were harvested 15 days post‑tumour inoculation. The expression levels of biomarkers related to epithelial‑mesenchymal transition (EMT) and molecules associated with CC‑chemokine receptor 10 (CCR10)‑mediated PI3K/Akt/GSK‑3β/Snail signalling were identified using reverse transcription‑quantitative PCR and western blotting. The results demonstrated that Plasmodium Infection significantly suppressed the progression, recurrence and metastasis of HCC in the two mouse models. The expression levels of E‑cadherin were significantly higher in the Plasmodium‑treated group compared with that in the control group, whereas the expression levels of Vimentin and Snail were significantly lower in the Plasmodium‑treated group. Furthermore, Plasmodium Infection inhibited the activation of Akt and GSK‑3β in the tumour tissues by downregulating the expression levels of CCR10 and subsequently suppressing the accumulation of Snail, which may contribute to the suppression of EMT and the prevention of tumour recurrence and metastasis. In conclusion, the results of the present study demonstrated that Plasmodium Infection inhibited the recurrence and metastasis and improved the prognosis of HCC by suppressing CCR10‑mediated PI3K/Akt/GSK‑3β/Snail signalling and preventing the EMT. These results may be important for the development of novel therapies for HCC recurrence and metastasis, especially for patients in the perioperative period.

Keywords

Plasmodium; hepatocellular carcinoma; metastasis; EMT.

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