The Study On The Expression Of FOXM1 In Small Cell Lung Cancer And Its Role In Lung Cancer Cell Proliferation And Invasion

PartⅠ:The study on the expression of FOXM1 in small cell lung cancer tissues[Objectives]To investigate the expression of FOXM1 in small cell lung cancer tissues.[Methods]37 small cell lung cancer tissues and 22 peritumoral and macroscopically normal lung tissues were collected to investigate their expression of FOXM1 with immuohistochemical methods.[Results]FOXM1 immuohistochemical staining results showed that of the 37 small cell lung cancer tissuses,6 showed strong staining,17 moderate staining,and 14 negative staining.The overall positive rate was 62.16%.While in the 22 control lung tissues 3 showed strong staining,4 moderate staining,and 15 negative staining. Its overall positive rate was 31.82%,which was significantly lower than SCLC tissues(χ~2=5.083,P=0.024).[Conclusions]The FOXM1 expression level of lung small cell lung cancer tissues was significantly elevated compared with the peritumoral normal lung tissues,which suggested that FOXM1 might play a role in the pathogenisis of small cell lung cancers. PartⅡ:Inhibition of FOXM1 expression leads to decrease of lung cancer cell proliferation and invasion ability[Objectives]To investigate the change of proliferation and invasion ability of non-small cell lung cancer(NSCLC) cell line SPC-A-1,A549,LTEP-a-2 and small cell lung cancer(SCLC) cell line H446 with FOXM1 expression deficiency.[Methods]A small interfering RNA targeting FOXM1 was designed to deplete the FOXM1 expression of these cell lines.Real-time RT-PCR and Western blot were used to examine the FOXM1 expression in mRNA and protein level,respectively.Colony assay,wound healing assay and transwell chamber assay were used to evaluate the colony formation ability and invasion ability of FOXM1 deficient cells.Cell cycle was examined using flowcytometry.[Results]The siRNA we designed could efficiently deplete FOXM1 expression by 83.89%,83.61%,88.56%and 93.21%in these cell lines respectively,as proved with Real-time RT-PCR and Western blot.Colony assay showed that the colony formation ability of FOXM1 deficient cells was inhibited by 38.83%,47.17%,53.32%and 34.57%(P＜0.01) in 4 cell lines,respectively.The cell migration and invasion ability of siFOXM1 group were dramatically inhibited,as manifested by wound healing assay and transwell chamber assay.The average invasion cell numbers of siFOXM transfected cells was 76.41%,89.29%,82.58%and 73.79%fewer than unrelated-siRNA transfected cells in 4 cell lines,respectively(P＜0.01). FOXM1 deficiency caused a cell accumulation in G0-G1 phase and a significant reduction by 50%(P＜0.01) in S phase cell number.[Conclusions]The proliferation and invasion ability of 3 NSCLC cell lines and 1 SCLC cell line were significantly inhibited after the FOXM1 gene expression was depleted,which suggested that inhibiting FOXM1 expression might be a promising way for lung cancer therapy.