Effects of Brusatol on the Proliferation, Migration, and Angiogenesis of Gastric Cancer MGC-803 Cells by Regulating the SHH/GLI Signaling Pathway
XIONG Yulong1, CHEN Bo2*
This article investigates the effects of BRU (Brusatol) on the proliferation, migration, and an giogenesis of gastric cancer MGC-803 cells by regulating the SHH/GLI signaling pathway. MGC-803 cells were cultured in vitro and treated with different concentrations of BRU to screen for drug action concentrations. The cells were separated into five groups: control group (Ctrl group), BRU low, medium, and high concentration groups (L BRU, M-BRU, H-BRU group, 200, 400, 800 nmol/L), and H-BRU+SHH activator group (H-BRU+PM group). EdU (5-ethynyl-2’-deoxyuridine) method was applied to detect cell proliferation. Flow cytometry was applied to detect apoptosis. Scratch healing assay was used to observe cell migration. Transwell chamber experiment was ap plied to detect the invasion. The vascular mimicry formation experiment was applied to observe the angiogenesis. The expression of SHH, GLI, VEGF (vascular endothelial growth factor), VEGFR2 (vascular endothelial growth factor receptor 2), PTCH1 (patched 1) and SMO (smoothened) were detected by Western blot. The results showed that 200, 400, 800 nmol/L were selected as the concentration of BRU for subsequent experiments. Compared with the Ctrl group, the percentage of EdU positive cells, scratch healing rate, and number of cell invasions, the number of lumens, and the protein expressions of SHH, GLI1, VEGF, and VEGFR2 in MGC-803 cells decreased in the L BRU, M-BRU, and H-BRU groups, while the apoptosis rate increased (P<0.05). PM weakened the effect of H-BRU on the above indicators in MGC-803 cells (P<0.05). The results indicated that brusatol may inhibit the proliferation, migration, invasion and angiogenesis of gastric cancer MGC-803 cells and promote cell apoptosis by suppressing the protein expression of SHH/GLI signaling pathway.
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