Objective  To explore the effects of resveratrol (RSV) on regulating the apoptosis, invasion ability and epithelial-meshenchymal transition (EMT) of GBC-SD cells and the underlying mechanisms.

Methods  GBC-SD cells were cultured in vitro, and randomly divided into blank group, RSV low, medium and high dose groups (0, 20, 50, 100 μmol·L^-1 RSV). Annexin V-FITC/PI double stain flow cytometry was used to analyze the cellular apoptosis, RT-PCR assay was used to test the mRNA expression level of Bcl-2, Bax and Caspase 3, Transwell invasion assay was used to test the invasion ability of GBC-SD cells, and Western blotting assay was used to detect the protein expression of EMT markers (E-cadherin, N-cadherin and Vimentin) and Hedgehog signaling members (Gli1, Gli2 and Shh). GBC-SD cells were then randomly divided into blank plasmid group, Gli1 overexpression plasmid group, and Gli1 overexpression plasmid+RSV group. The overexpression of Gli1 protein was detected by Western blotting, and the apoptosis rate and invasion ability were detected in the above group by Annexin V-FITC/PI double stain flow cytometry and transwell invasion assay respectively.

Results  Compared with the blank group, the apoptosis rate, Bax and Caspase 3 mRNA expression in each RSV dose group were significantly increased (P<0.05 or P<0.01), and the cell invasion ability was significantly reduced (P<0.01); the expression of Bcl-2 mRNA in the middle and high dose groups of RSV significantly decreased (P<0.01). Compared to the blank group, the protein expression level of E-cadherin was significantly increased, while the protein expression level of N-cadherin, Vimentin, Gli1, Gli2 and Shh were significantly decreased in the high-dose group of RSV (P<0.01). Compared with the transfected empty plasmid+RSV group, the apoptosis rate of cells in the Gli1 overexpression plasmid+RSV group was reduced and the invasion ability was increased (P<0.001).

Conclusion  RSV promotes GBC-SD cell apoptosis, inhibits GBC-SD cell invasion and EMT, and its mechanism of action may be related to the inhibition of Hedgehog signaling.

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