The Effects of 2,2',4'-Trihydroxychalcone on the Cell Proliferation, Metastasis, and Apoptosis in Human Lung Cancer Cell Line A549

Objectives：Our study aimed to evaluate the antitumor effects of 2,2',4'-trihydroxychalcone (7a) on human lung cancer cell line A549. Methods：A549 cells were treated with different concentrations of 7a for different times. The cells without 7a were set as the negative control group. The cell proliferation, invasion, vasculogenic mimicry (VM) formation, heterogeneous adhesion, apoptosis were, respectively, measured by CCK-8, transwell invasion assay, vasculogenic mimicry assay, adhesion assay and flow cytometry. In addition, the expression of related proteins were examined via western blot or ELISA. Results：Our research found that 7a had a significant inhibitory effect on the survival rate of lung cancer A549 cells, while almost had no effect on human lung epithelial BEAS-2B cells and human venous endothelial cells (HUVECs). The migration rate, VM length, invasion and heterogeneous adhesion number of cells treated with 7a significantly decreased as the increase in concentration, while the apoptosis rate increased. Western blot analysis showed that 7a treatment significantly upregulated the expression of E-cadherin, cleaved PARP, Bax, caspase-3, and simultaneously downregulated the expression of MMP-2/9, Bcl-2, p-PI3K, p-Akt, p-MTOR, VEGF, E-selectin and N-cadherin. At the same time, ELISA results found that the pro-angiogenic factor VEGF level in culture media was reduced in the presence of 7a. Additionally, 7a could also reduce the nucleus NF-κB protein level, which would inhibit gene transcription of tumor activity-related proteins. Conclusion：7a might exert inhibitory effects on A549 cells via inhibiting cell proliferation, migration, VM formation, heterogeneous adhesion and inducing apoptosis through suppressing the PI3K/AKT/NF-κB signaling pathway, suggesting that 7a might have therapeutic potential for the treatment of lung cancer.