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OBJECTIVE To investigate the synergistic effect and mechanism of curcumin （CUR） combined with zerumbone （ZER） on the biological behavior of non-small cell lung cancer （NSCLC） A549 cells. METHODS CCK-8 method and Gin’s formula were used to screen the optimal concentration combination for synergistic effect after the combination of CUR and ZER. The cells were divided into blank group， CUR group， ZER group， and CUR+ZER group. Flow cytometry was used to evaluate cell apoptosis， and clone formation experiment was used to evaluate cell proliferation ability， scratch experiment and Transwell migration experiment were used to evaluate cell migration ability， and Transwell invasion experiment was used to evaluate cell invasion ability. Western blot assay was used to detect the protein expressions of phosphorylated phosphatidylinositol-3-kinase （p- PI3K）， phosphorylated protein kinase B （p-Akt）， and vascular endothelial growth factor A （VEGF-A）. RESULTS The half inhibitory concentrations of CUR and ZER on A549 cells were approximately 16 and 12 μmol/L， respectively； the drug combination of CUR 8 μmol/L+ZER 6 μmol/L had the highest efficiency enhancement index， with the cell proliferation inhibition rate of （77.41±4.16）%， indicating the most significant synergistic effect. Compared with the CUR and ZER groups， the cell apoptosis rate in the CUR+ZER group was significantly increased （P＜0.01）， while the cell clone formation rate， cell migration rate， the number of migrating cells， the number of invading cells， and relative expression levels of p-PI3K， p-Akt， and VEGF-A proteins in the cells were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The combination of CUR and ZER has a synergistic effect， significantly promoting the apoptosis of NSCLC cells， and inhibiting cell proliferation， migration， and invasion. Its potential mechanism may be closely related to the inhibition of the PI3K/Akt signaling pathway， thereby down-regulating the protein expression of VEGF-A.
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Objective To investigate the expression of DNMT3b and its correlation with clinicopathological parameters of pancreatic cancer.Methods The expressions of DNMT3b protein in 12 pancreatic cancer tissues and para-cancerous tissues were detected by Western blot.The expressions of DNMT3b protein in 59 pancreatic cancer tissues were detected by immunohistochemistry.The association of DNMT3b expression and clinicopathological parameters of pancreatic carcinoma were analyzed.Results Western blot results showed the expressions of DNMT3b protein in pancreatic cancer tissues and para-cancerous tissues were 0.69 ±0.13and 0.14 ±0.03,and the protein level of DNMT3b in pancreatic cancer tissues were significantly higher than that in para-cancerous tissues (t =4.464,P ＜0.05 ).Immunohistochemistry examination showed that the positive rates of DNMT3b protein were 59％ in pancreatic cancer tissues and negative in para-cancerous tissues.DNMT3b expression was positively correlated with the TNM stage and lymph node metastasis.Conclusions DNMT3b is highly expressed in pancreatic cancer tissues,and it is related with malignant biological behaviors of pancreatic cancer cells.
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Objective To investigate the correlation between the ratio change of circulating myeloid-derived suppressor cells (MDSCs) and cellular immune function in healthy volunteers,chronic gastritis patients,gastric intraepithelial neoplasia patients and gastric cancer patients.Methods From February 2011 to July 2011,129 peripheral blood samples were collected,including 32 healthy volunteers,48 chronic gastritis patients,27 gastric intraepithelial neoplasia patients and 22 gastric cancer patients.The percentages of peripheral blood MDSC,T lymphocyte subsets and regulatory T cells (Treg) were determined by flow cytometry.The data were analyzed by one way analysis of variance,pearson and spearman correlation.Results The percentages of circulating MDSC,CD8+ T lymphocyte and Treg were highest in gastric cancer patients (9.63％±3.24％,10.03％ ± 1.26％,69.45％±3.42％) and lowest in healthy volunteers (0.92％±0.33％,4.12％ ±0.99％,32.35％ ±4.83％).Those of gastric intraepithelial neoplasia patients (5.13％ ± 1.30％,7.54％ ± 0.79％,53.26％±4.30％) were lower than gastric cancer patients but higher than chronic gastritis patients (2.76％ ±0.64％,6.28％ ±0.61％,42.37％ ±4.02％).The differences among each groups were statistically significant (F=24.85,20.88,37.84,all P＜0.05).However,the percentage of circulating CD4+T lymphocyte was highest in healthy volunteers (65.10％±4.10％),55.15％ ± 4.00％ in chronic gastritis group,42.23％ ± 3.91％ in gastric intraepithelial neoplasia group,and lowest in gastric cancer group (26.84％ ± 3.69％).The differences among each groups were statistically significant (F=46.80,P＜0.05).A significant correlation between circulating MDSC and TNM stages of gastric cancer was also observed (r=0.856,P＜0.01).The percentage of circulating MDSC was positively correlated with Treg percentage (r =0.862,P ＜ 0.01),and negatively correlated with CD4+/CD8+ ratio (r=-0.768,P＜0.01).Conclusion The increase of MDSC percentage in peripheral blood is correlated with human cellular immune function,which might play an important role in the tumor immune evasion during the development of gastric cancer.