@article {Xu389, author = {Nuo Xu and Chunxue Bai}, title = {Gefitinib selectively targets non-small cell lung cancer cells through inhibition of Forkhead box M1}, volume = {38}, number = {Suppl 55}, elocation-id = {389}, year = {2011}, publisher = {European Respiratory Society}, abstract = {Rationale: Gefitinib shows dramatic treatment effects in non-small cell lung cancer (NSCLC) patients. But only about 20\% of such patients are benefited. Why the remainder derives no such effect is only partly understood. FoxM1 has been shown to be overexpressed in NSCLC. Therefore, we assessed the effect of FoxM1 on the response of lung cancer cell line to gefitinib and examined the possible mechanism.Method: Expression levels of FoxM1 and downstream targets were measured by RT-PCR and immunoblotting in gefitinib sensitive and resistant NSCLC cells lines H292 and SPC-A-1. A H292 cell line with constitutively active FoxM1 mutant (N-FoxM1 group)was established. MTT assay and FCM were used to detect the cell survival and apoptosis in N-FoxM1 and vehicle groups.Results: The mRNA levels of FoxM1 in SPC-A-1 cells at 24, 48 and 72 hours after incubation of gefitinib increased by 38\%, 53\%, 72\%, while reduced by 23\%, 46\%, 54\% in H292 cells with 10 uM and 1 μM of gefitinib. The survival rates of N-FoxM1 and vehicle groups with incubation of 1, 0.5 and 0.1μM of gefitinib for 3 days are 65.34\%, 73.8\%, 93.17\%, and 50.62\%, 60.59\%, 80.53\%. The apoptosis rates of both groups are 7.39\%, 3.84\% and 18.97\%, 13.85\% with treatment of 1uM and 0.1 μM gefitinib. The mRNA expression level of FoxM1 downstream targets aurora kinase B, SKP2, PLK1, CDC25B, survivin and cyclinB1 were increased in SPC-A-1 cells with gefitinib treatment. Moreover, the increased protein level of survivin and cyclinB1 were further confirmed by immunoblotting.Conclusion: These data suggest that FoxM1 confers the resistance of lung cancer cells to gefitinib. Thus, FoxM1 could be used as a therapeutic target of gefitinib resistance.}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/38/Suppl_55/389}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }