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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. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Scutellarin (Scu) and caffeic acid ester fraction (Caf), the extracts from the traditional Chinese herb, Erigeron breviscapus, are known to ameliorate post ischemic neuronal dysfunction. Aim of the study: Neurotrophic factors (NTFs) are essential for neuronal growth and survival. We explored the neuroprotective effect of Scu and Caf by synthesis and release of NGF, BDNF and GDNF in rat astrocytes exposed to hypoxia/reoxygenation and MACO rats. And the neuroprotection of Scu and Caf was also explored. Materials and methods: The primary rat astrocytes were cultured in vitro. The temporal mRNA and protein expression profile during hypoxia/reoxygenation were analyzed using real-time RT-PCR and ELISA. The expression of p-CREB, p-Akt, p-MAPKs and Bax were analyzed by western blotting. Cell viability of neuro-2A was measured using CCK-8 and cell cytotoxicity was measured with LDH release. Results: During hypoxia/reoxygenation a similar decrease pattern of NTFs (NGF, BDNF and GDNF) was observed in both mRNA and protein; Scu and Caf enhanced the expressions of NGF, BDNF and GDNF mRNA and protein in astrocytes under hypoxia/reoxygenation condition. CREB and Akt, but not MAPKs ( p-JNK, p-ERK1/2 and p-38) may be involved in the expression of NTFs. Concomitantly, conditioned medium from astrocytes which was treated by Scu or Caf after hypo3h/Reox24h significantly reduced neurotoxicity compared with conditioned medium from hypo3h/Reox24h astrocytes alone, and they show the tendency of increased neurons viability accompanied with Bax changes. Conclusions: These results indicate that the neuroprotective effect of Scu and Caf might be mediated, at least in part, via a stimulation of the production and release of NTFs through p-CREB and p-Akt signaling. Furthermore, Scu and Caf could antagonistic the hypoxia induced toxicity through astrocytes conditioned medium. Those results suggested that Scu and Caf might have therapeutic potential for stroke. [Copyright &y& Elsevier]