ABSTRACT
BACKGROUND@#Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear.@*METHODS@#An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting.@*RESULTS@#The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.@*CONCLUSIONS@#PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.
ABSTRACT
Aim To investigate the effect of fibrinogenlike protein 1 (FGL1)) silencing on docetaxel sensitivity in human lung adenocarcinoma PC-9 cells. Methods Western blot was used to detect the expression of FGL1 protein in human normal bronchial epithelial cell line BEAS-2B and human lung adenocarcinoma cell line PC-9. The FGL1 gene in PC-9 cell line was silenced by siRNA. CCK-8 assay was used to detect the inhibitory effect of silencing FGL1 on PC-9 cell proliferation and its effect on docetaxel sensitivity. Results Compared with BEAS-2B cell line, FGL1 was highly expressed in PC-9 cell line, and the relative expression of FGL1 protein was 6. 5 times that of BEAS-2B cell line with statistically significant difference (P <0. 01). Silencing FGL1 by transfection with FGLlsiRNA could enhance the inhibitory effect of docetaxel on PC-9 cells. Compared with FGLlsiNC group, the IC50value of PC-9 cells in FGL1siRNA group was significantly reduced with statistically significant difference (P < 0. 01). Conclusions Specific silencing of FGL1 gene could inhibit the expression of FGL1 in human lung adenocarcinoma cell PC-9, inhibit the proliferation of PC-9 cells and increase the sensitivity to docetaxel.
ABSTRACT
OBJECTIVE@#To investigate the role of myeloid-derived suppressor cells (MDSC) in the prognosis of patients with diffuse large B cell lymphoma (DLBCL).@*METHODS@#The peripheral blood of 52 DLBCL patients and 30 healthy volunteers was collected. The CD14HLA-DR was used as the immune marker for MDSC. The role of MDSC in the prognosis of DLBCL patients was analyzed by combination with the related clinicopathological data.@*RESULTS@#The proportion of MDSC in peripheral blood of newly diagnosed DLBCL patients increased significantly (P＜0.01). The expression of MDSC in DLBCL patients was related with clinical staging, lactate dehydrogenase (LDH) level and IPI score (P＜0.01). There was no significant correlation with sex, age, and B symptoms. Univariate analysis showed that the clinical stage, serum LDH level, IPI score and MDSC level were the adverse factors affecting the overall survival (OS). Multivariate analysis showed that IPI score and MDSC level were independent risk factors for OS in DLBCL patients.@*CONCLUSION@#MDSC can be used as an important index to evaluate the prognosis of DLBCL patients, contributing to evaluate the immune and tumor microenvironment of DLBCL patients.
Subject(s)
Humans , Biomarkers , HLA-DR Antigens , Lipopolysaccharide Receptors , Lymphoma, Large B-Cell, Diffuse , Myeloid-Derived Suppressor Cells , Prognosis , Tumor MicroenvironmentABSTRACT
<p><b>BACKGROUND</b>Lumiracoxib is a highly selective cyclooxygenase-2 (COX-2) inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestinal safety. No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.</p><p><b>METHODS</b>The antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Drug-drug interactions were analyzed using the coefficient of drug interaction (CDI) to characterize the interactions as synergism, additivity or antagonism. Morphological changes were observed by acridine orange fluorescent staining. Extent of apoptosis was determined by flow cytometry.</p><p><b>RESULTS</b>Lumiracoxib (15 - 240 micromol/L) has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the IC50 values of 2597 micromol/L and 833 micromol/L, respectively. The synergistic effect was prominent when lumiracoxib (15 - 240 micromol/L) was combined with docetaxol (0.2 - 2 micromol/L) (CDI < 1). Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells. Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.</p><p><b>CONCLUSIONS</b>Lumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol, which may be related to apoptotic induction and cell cycle arrest.</p>