Contribution of Epstein-Barr virus infection to chemoresistance of gastric carcinoma cells to 5-fluorouracil
Research Institute of Immunobiology, Department of Medical Lifescience, College of Medicine, Catholic University of Korea, Seoul, 137-701, Korea.Archives of Pharmacal Research (Impact Factor: 2.05). 04/2011; 34(4):635-43. DOI: 10.1007/s12272-011-0414-7
Although Epstein-Barr virus (EBV) is associated with 6-16% of the gastric carcinoma (GC) cases, the effect of EBV infection on the tumorigenesis process and the responsiveness to chemotherapy remain unclear. We compared chemosensitivity of the EBV-positive GC (AGSEBV) and EBV-negative GC (AGS) cells to 5-fluorouracil (5-FU). Although 5-FU inhibited the growth of both cell lines in a dose- and time-dependent manner, the sensitivity of EBV-positive GC cells to 5-FU was lower than that of EBV-negative GC cells. The cleavage of PARP and caspase-3 was also lower in AGS-EBV cells than in AGS cells following 5-FU treatment. Both the level of Bcl-2 expression and the ratio of Bcl-2/Bax were higher in AGS-EBV than in AGS cells not only at basal state but also following 5-FU treatment. Moreover, p53 and p21 expression was enhanced further by 5-FU in AGS than in AGS-EBV cells. Immunofluorescence assay and Western blot showed that 5-FU induced the expression of EBV-lytic genes including BZLF1, BRLF1, BMRF1 and BHRF1. Our results suggest that latent and lytic EBV infection contributes to the chemoresistance to 5-FU in gastric carcinoma by modulating apoptosis related cellular genes.
- [Show abstract] [Hide abstract]
ABSTRACT: Periostin is frequently upregulated in human cancers including gastric cancer and implicated in cancer cell proliferation, invasion, and epithelial-mesenchymal transition. This study was undertaken to investigate the effects of periostin overexpression on the chemosensitivity of gastric cancer cells. We constructed a stable cell line overexpressing periostin in SGC-7901 human gastric cancer cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed that periostin had no influence on the proliferation of SGC-7901 cells. Compared to empty vector-transfected cells, overexpression of periostin rendered SGC-7901 cells more resistant to cisplatin or 5-fluorouracil (5-FU)-induced apoptosis, accompanying with less release of cytochrome c from mitochondria and diminished cleavage of caspase-3 and poly (ADP-ribose) polymerase. Periostin-overexpressing cells treated with cisplatin or 5-FU showed significantly (p < 0.05) decreased expression of Bax and p53 proteins and increased expression of Bcl-2 protein, when compared to drug-treated mock counterparts. Restoration of p53 expression by delivering wild-type p53 gene resulted in a marked increase in drug-induced apoptosis in periostin-overexpressing SGC-7901 cells. Periostin overexpression elevated the phosphorylation of Akt. Pretreatment of periostin-overexpressing cells with an Akt inhibitor, MK-2206, partially rescued periostin-mediated inhibition of p53 expression and drug resistance. Taken together, our data indicate that periostin confers protection against cisplatin or 5-FU-induced apoptosis in SGC-7901 cells, likely through modulating the Akt/p53 pathway, and thus represents a potential therapeutic target in gastric cancer.Molecular Biology Reports 10/2012; 40(2). DOI:10.1007/s11033-012-2218-3 · 2.02 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Nobiletin is a typical polymethoxyl flavone from citrus fruits that has anticancer properties, but the molecular mechanism of its inhibitory effects on the growth of p53-mutated SNU-16 human gastric cancer cells has not been explored. In this study, nobiletin was found to be effective at inhibiting the proliferation of SNU-16 cells than other flavonoids. Nobiletin induced the death of SNU-16 cells through apoptosis, as evidenced by the increased cell population in the sub-G1 phase, the appearance of fragmented nuclei, an increase in the Bax/Bcl-2 ratio, the proteolytic activation of caspase-9, an increase in caspase-3 activity, and the degradation of poly(ADP-ribose) polymerase (PARP) protein. We found that the combination of nobiletin plus the anticancer drug 5-fluorouracil (5-FU) reduced the viability of SNU-16 cells in a concentration-dependent manner and exhibited a synergistic anticancer effect (combination index = 0.38) when 5-FU was used at relatively low concentrations. The expression of p53 protein increased after treatment with 5-FU, but not nobiletin, whereas the expression of p21 (WAF1/CIP1) protein increased after treatment with nobiletin, but not 5-FU. The cellular responses to nobiletin and 5-FU occurred through different pathways. The results of this study suggest the potential application of nobiletin to the enhancement of 5-FU efficiency in p53 mutant tumors.Nutrition and Cancer 02/2013; 65(2):286-95. DOI:10.1080/01635581.2013.756529 · 2.32 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: A novel three-dimensional biodegradable micro-device using microelectromechanical systems technology was developed for implantable controlled drug delivery. In order to evaluate the effect of monomer composition and molecular weight of poly(lactic-co-glycolic acid) (PLGA) on the drug release, three 5-Fluorouracil loaded micro-devices, made of 50/50, 27 kDa; 50/50, 40 kDa and 75/25 27 kDa PLGA, were prepared and characterized by in vitro and in vivo methods. The in vitro drug release from three micro-devices followed zero-order kinetics, and PLGA micro-device with the higher molecular weight and lactide/glycolide ratio tended to a longer sustained release period. The in vivo release results agreed with the in vitro results and drug release in vivo was faster than that in vitro for each of micro-devices. And three micro-devices showed different tumor inhibition effect in the tumor bearing mice. In addition, the SEM and weight loss experiments showed that PLGA micro-devices with lower molecular weight and lactide/glycolide ratio had faster degradation. These data provided the information for the optimization of the novel three-dimensional biodegradable micro-device to obtain more suitable systems for controlled release and to meet release requirements of different drugs.Archives of Pharmacal Research 06/2013; 36(12). DOI:10.1007/s12272-013-0168-5 · 2.05 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.