Licochalcone A Inhibits Proliferation and Metastasis of Colon Cancer by Regulating miR-1270/ADAM9/Akt/NF-κB axis

Abstract

Background: We aimed to explor the therapeutic effect and molecular mechanism of licochalcone A (LCA) on colon cancer. Methods: This study was carried out in 2020-2021 in Nanjing Tongren Hospital, China. Colon cancer HCT116 cells were treated with different concentrations of LCA. Cell counting kit-8, colony formation and flow cytometry assays were used to analyze cell viability, proliferation and apoptosis. Wound healing and transwell experiments were used to measure cell migration and invasion ability. The expression of ADAM9 and apoptosis-related proteins in different LCA treatment groups was detected by western blot. HCT116 cells were transfected with ADAM9 small interfering RNAs (siRNAs) or overexpression vectors. The database screened the upstream miRNA targeting ADAM9 and predicted the targeted binding site between miR-1270 and ADAM9, which was verified by a dual-luciferase reporter assay. Rescue experiments were performed to confirm the effects of the miR-1270/ADAM9 axis on cell proliferation and metastasis. Results: LCA decreased cell growth (P<0.05), migration (P<0.05), and invasion (P<0.05) of colon cancer cells and inhibited ADAM9 expression in a dose-dependent manner. LCA affected the functions of colon cancer cells by negatively regulating the expression of ADAM9. MiR-1270, increased by LCA, targeted and suppressed ADAM9 expression significantly (P<0.001). ADAM9 overexpression restrained miR-1270 mimic and LCA-induced changes in cell proliferation, migration, and invasion, and promoted apoptosis in HCT116 cells significantly (P<0.01). LCA and miR-1270 mimic inactivated the Akt/NF-κB pathway, while ADAM9 overexpression rescued it. Conclusion: LCA exhibited antitumor efficacy in HCT116 cells by inhibiting the Akt/NF-κB signaling pathway by regulating the miR-1270/ADAM9 axis.