β-carotene Regulates the Murine Liver Microenvironment of a Metastatic Neuroblastoma

BACKGROUND: The anticarcinogenic effects of β-carotene (BC) have been well-characterized. However, the effect of BC on the microenvironment of a tumor remains to be investigated, especially since normal tissue proximal to a tumor has been shown to play a critical role in cancer progression and metastasis. For young children, neuroblastoma (NB) is the most common extracranial solid cancer diagnosed. Therefore, in the present study, effect of BC on the murine liver microenvironment of a metastatic NB was evaluated. METHODS: Using a mouse model, three experimental groups were established: control mice, mice receiving an injection of SK-N-BE(2)C cells (TC), and mice receiving an injection of SK-N-BE(2)C cells plus 2 mg/kg BC twice a week (BC). Eight weeks after the injection of tumor, liver tissues were collected from all three groups, with the TC and BC tissues collected proximal to the metastatic NBs. RESULTS: Compared to control tissues, BC tissues exhibited lower levels of proliferation, apoptosis, and metastasis. Assays for these processes included the detection of lower levels of proliferating cell nuclear antigen (PCNA), Bax, MMP2, and MMP9. In addition, higher levels of Bcl-2 were detected. Fewer cells undergoing an epithelial mesenchymal transition (EMT) were also observed in the BC group. Furthermore, BC tissues were associated with reduced expression of cancer stem cell marker, delta-like 1 homologue (DLK1), lower levels of VEGF mRNA and fewer CD31-positive cells. Finally, The antioxidant capability of the tumor microenvironment for the BC group was enhanced with higher expression levels of glutathione peroxidase (GPX), catalase, and manganese superoxide (MnSOD) detected. CONCLUSION: These data suggest that BC affects the microenvironment of a tumor, and this enhances the anti-cancer effects of BC.