Inhibitory Effects Of XAV939 On Small Cell Lung Cancer H446 Cells Proliferation And Wnt/?-catenin Signaling Pathway In Vitro

Objects: Lung cancer,including small cell lung carcinoma(SCLC)and non-small cell lung carcinoma(NSCLC),as the most common tumor types,represents 13% of newly diagnosed cancers worldwide.SCLC represents 15% of all lung cancer cases.But almost no major breakthrough in SCLC over the last 30 years.Wnt signaling pathway which is associated with many kinds of tumor types,plays a key role in tumor progression and metastasis.In the present study,we investigated the effects of XAV939 on cell proliferation and Wnt/?-catenin signaling pathway of H446 cells.All of these results may provide a potential therapeutic approaches for treating SCLC.Methods: In vitro,H446 cells were cultured with different concentrations of sole medication XAV939,cisplatin and united medication.The inhibition of cell proliferation was tested by CCK-8.The m RNA expression of ?-catenin and Cyclin D1 were measured by reverse transcription-PCR(RT-PCR)and the protein expression of ?-catenin,Cyclin D1 by Western blotting.Results: We found that XAV939 could inhibit cell proliferation of SCLC in a dose-dependence manner(P<0.01),without time-dependence manner(P>0.05)while DDP did in a time-and dose-dependent manner(P<0.01).And the treatment combining XAV939 with DDP resulted that their combinatorial effects were antagonism at low-dose and synergistic at high-dose.We also found that the m RNA and protein expression of?-catenin and Cyclin D1 were significantly lower in SCLC cell lines with XAV939 treatment than that in control group.And the levels of gene and protein expression were in a dose-dependence(P<0.05).Conclusion:These findings suggested that XAV939 could inhibit proliferation of H446 cells,at least partially,through down-regulating Wnt/?-catenin signaling pathway.