抄録
Background: The dietary flavonoids luteolin and quercetin are reported to inhibit growth and metastasis of cancer cells. S100A7 was highly expressed in cancer cells and related to tumor malignancy. In our previously reports, we found luteolin and quercetin could reduce metastasis of cancer cells through Src/FAK/Cortatin signaling in high invasive A431-III cancer model. S100A7 was also higher expressed in A431-III cells. The inhibition effect and mechanism of luteolin and quercetin on S100A7 is unclear. Here, we investigate the effect and inhibition mechanism of luteolin and quercetin on S100A7 in A431-III cancer cell model.
Methods: Luteolin, quercetin and Src inhibitor SU6066 and Stat3 inhibitor S3I-201 are used to analyze activation signaling of S100A7 in highly invasive A431-III and A431-P cells. Knockdown S100A7 by shRNA and overexpression of S100A7 are used to analyze metastasis ability of cancer cells activated by S100A7. Luciferase assay was used to analyze the transactivation ability of S100A7 activated by Src/Stat3 signaling. MTT assay was used to analyze the cell viability of A431-III cells by treated with drugs. The wound-healing and invasion assay are used to analyze metastasis ability of A431-III cells. The western blot and qPCR experiment are used to analyze protein and mRNA levels.
Results: S100A7 is highly expressed in A431-III cells than in parental A431-P cells. Treatment with luteolin and quercetin in A431-III cells reduced phosphorylation of Src/Stat3 signaling. The mRNA and protein level of S100A7 expression was also reduced. Treatment with Src and Stat3 inhibitors were also decreased expression of S100A7. Transactivation ability of S100A7 promoter was reduced by Src and Stat3 inhibitor and activated by Stat3. Treatment with luteolin, quercetin, SU6066, S3I-201 reduced migration and invasion ability of A431-III cells. Knockdown S100A7 decreased migration and invasion ability of cancer cells and overexpression of S100A7 shown opposite results.
Conclusion: These data suggest that luteolin and quercetin inhibit activation of Src/Stat3/S100A7 signaling to reduce metastasis ability of A431-III cells. S100A7 shows a potential role as a cancer marker and therapy target in cancer cells.
