The Wnt Inhibitor XAV939 Suppresses Small Cell Lung Cancer H446 Cells Proliferation And Induces Apoptosis

Objects: Small cell lung cancer(SC LC) is the most aggressive type of lung cancer because of the fast tumor doubling time and early haematogenous spread. Wnt signaling pathway is frequently associated with tumor progression and metastasis. Inhibition of Wnt/β-catenin signaling therefore is an attractive strategy for anticancer drugs. In this study, we aimed to investigate the potential of XAV939 in suppressing small cell lung cancer cells( SC LC) growth,and to explore the mechanism by apoptosis analysis and cell cycle analysis.Methods: MTT assays was used to detect the growth inhibition rate of cells in each group, and to explore the best cell growth inhibition of drug concentration. Flow cytometry was used to detect the impact of XAV939 effects on cell cycle and apoptosis.Results: We found that XAV939 inhibited the growth of H446 in a dose-dependent manner(P<0.01), but cisplatin did in a time- and dose-dependent manner( P<0.05). The two-drug combination group had more pronounced inhibition of cell growth in at high dose. In addition, XAV939 markedly induced cell apoptosis of SC LC cell line H446 by increasing G0/G1 phase proportion(P<0.05) and decreasing S and G2/M phase proportion(P<0.05). The percentage of apoptotic H446 cells increased with XAV939 dosage(P<0.05).Conclusion:All these findings indicate that XAV939 is able to inhibit SCLC H446 cell growth by inducing cell apoptosis and leading to G0/G1 cell inhibition through Wnt pathway, and therefore may prove to be an adjuvant to the treatment of SCLC.