Sulforaphane is a common antioxidant selectively abundant in cruciferous plants, which exhibits effective anti-cancer actions in control of tumorigenesis or progression of various cancers. A recent study has shown that sulforaphane attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC), suggesting its potential anti-metastatic effects. In this study we assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in human NSCLC cell lines H1299, 95C and 95D with IC 50 values of 9.52±1.23, 9.04±1.90 and 17.35±2.03 μmol/L, respectively. At low concentrations (1-5 μmol/L), sulforaphane dose-dependently inhibited the migration and invasion of 95D and H1299 cells with relatively high metastatic potential. The anti-metastatic action of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3 NSCLC cell lines were correlated with their metastatic ability, and were decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo. Further studies revealed that miR-616-5p directly targeted GSK3β and decreased its expression, whereas sulforaphane decreased miR-616-5p levels by histone modification, and followed by inactivation of the GSK3β/β-catenin signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically utilized as a biomarker or therapeutic target to inhibit metastasis.

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Microvascular compression of the trigeminal root entry zone (TREZ) is the main cause of most primary trigeminal neuralgia (TN), change of glial plasticity was previously studied in the TREZ of TN rat model induced by chronic compression. To better understand the role of astrocytes and immune cells in the TREZ, different cell markers including glial fibrillary acidic protein (GFAP), complement C3, S100A10, CD45, CD11b, glutamate-aspartate transporter (GLAST), Iba-1 and TMEM119 were used in the TN rat model by immunohistochemistry and flow cytometry. On the post operation day 28, GFAP/C3-positive A1 astrocytes and GFAP/S100A10-positive A2 astrocytes were activated in the TREZ after compression injury, there were no statistical differences in the ratios of A1/A2 astrocytes between the sham and TN groups. There was no significant difference in Iba-1-positive cells between the two groups. The ratios of infiltrating lymphocytes (CD45+CD11b−) (p = 0.0075) and infiltrating macrophages (CD45highCD11b+) (p = 0.0388) were significantly higher than those of the sham group. In conclusion, different subtypes A1/A2 astrocytes in the TREZ were activated after compression injury, infiltrating macrophages and lymphocytes increased, these neuroimmune cells in the TREZ may participate in the pathogenesis of TN rat model.

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