ABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of forkhead box M1 (FOXM1) and its correlation with clinicopathological features and prognosis in patients with non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The expression of FOXM1 in 68 cases of NSCLC was detected by immunohistochemistry. The FOXM1 expression in 6 tumor tissues (3 cases with negative and 3 cases with positive expression of FOXM1) was analyzed by Western blotting to confirm the immunohistochemical results. The correlation of the expression of FOXM1 with clinicopathalogical features and overall survival of the NSCLC patients was analyzed.</p><p><b>RESULTS</b>The expression of FOXM1 protein was detected in the nuclei or cytoplasms of the tumor cells. The positive expression rate of FOXM1 was 36.8% (25/68). Western blotting confirmed the immunohistochemical results. The expression level of FOXM1 in advanced stage cancer was significantly higher than that in early stage NSCLC (P = 0.001). The median OS was 23.0 months in patients with negative expression of FOXM1 and 13.0 months in those with positive expression (P = 0.001). Univariate analysis revealed that histological grade, lymph nodes status, TNM stage and FOXM1 expression were significantly associated with prognosis in the NSCLC patients (P < 0.05). The Cox multivariate analysis demonstrated that lymph nodes status, TNM stage and FOXM1 expression were independent poor prognostic factors (P < 0.05).</p><p><b>CONCLUSION</b>The expression status of FOXM1 in NSCLC is an independent prognostic factor and negatively correlated with prognosis.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Follow-Up Studies , Forkhead Box Protein M1 , Forkhead Transcription Factors , Metabolism , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Lung Neoplasms , Metabolism , Pathology , Lymphatic Metastasis , Neoplasm Grading , Neoplasm Staging , Proportional Hazards ModelsABSTRACT
<p><b>OBJECTIVE</b>The aim of this study was to investigate the changes in mTOR activity and survivin expression in liver cancer cell line HepG2 cells treated with tamoxifen.</p><p><b>METHODS</b>Survivin transcription level and p70S6K was demonstrated by PCR, dual-luciferase reporter assay and Western blot analysis, respectively, and the apoptosis in the HepG2 cells was detected by flow cytometry.</p><p><b>RESULTS</b>Tamoxifen leads to apoptosis of the cells and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6K. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduced the survivin protein level but not affected the survivin transcription, indicating that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells.</p><p><b>CONCLUSIONS</b>Our results suggest that tamoxifen down-regulates survivin expression in HepG2 cells and it is mediated by transcriptional and post-transcriptional level via PI3K/Akt/mTOR pathway to induce apoptosis.</p>
Subject(s)
Humans , Antibiotics, Antineoplastic , Pharmacology , Antineoplastic Agents, Hormonal , Pharmacology , Apoptosis , Cell Proliferation , Down-Regulation , Drug Synergism , Hep G2 Cells , Inhibitor of Apoptosis Proteins , Genetics , Metabolism , Phosphatidylinositol 3-Kinases , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , RNA, Messenger , Metabolism , Ribosomal Protein S6 Kinases, 70-kDa , Metabolism , Signal Transduction , Sirolimus , Pharmacology , TOR Serine-Threonine Kinases , Metabolism , Tamoxifen , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To determine the expression level changes of survivin, a inhibitor of apoptosis protein, followed by activation of insulin receptors in human hepatocellular carcinoma HepG2 cell line, and to investigate the signalling pathway involved in the regulation.</p><p><b>METHODS</b>Human hepatocellular carcinoma HepG2 cells were treated with insulin alone or pre-treated with LY294002, a specific inhibitor of PI3K signalling pathway, to determine whether blocking PI3K signaling can attenuate the up-regulation of survivin expression. Real time RT-PCR and Western blot analysis were used to measure survivin mRNA and protein changes before and after treatment, respectively.</p><p><b>RESULTS</b>Without serum supplement, HepG2 cells expressed a small amount of survivin. Insulin induced survivin expression in a dose- and time-dependent fashion. Survivin expression was blocked if cells were pre-treated with LY294002 prior to insulin stimulation.</p><p><b>CONCLUSION</b>Insulin induces survivin expression via PI3K signalling pathway, suggesting that to interfere the key gene in this signalling pathway may block survivin expression, therefore, promoting apoptosis in hepatocellular carcinoma cells.</p>