Project description:Here we report that piroxicam/cisplatin combined treatment exerts an apoptotic effect on mesothelioma cells. Genome-wide transcriptome analyses lead us to identify p21 as the possible apoptosis mediator acting as downstream target of the piroxicam/cisplatin treatment.
Project description:Here we report that piroxicam/cisplatin combined treatment exerts an apoptotic effect on mesothelioma cells. Genome-wide transcriptome analyses lead us to identify p21 as the possible apoptosis mediator acting as downstream target of the piroxicam/cisplatin treatment. To analyze the potential therapeutic effect of the piroxicam/cisplatin treatment at molecular level, and to identify gene expression pattern modifications following the combined treatment, we performed a transcriptional profiling on HGU133A arrays, using cells treated with piroxicam, cisplatin or with piroxicam and cisplatin, choosing the time exposures in which apoptosis induction was absent or evident (8 and 24 hours). Biological duplicates or triplicates were generated for each prototypic situation and data were analyzed using the oneChannelGUI Bioconductor package (Sanges et al., 2007), comparing untreated cells with cells treated in single or combined treatment. After quality controls, the complexity of the data set was reduced removing the non-significant probe sets, resulting in a total of 4,247 out of the 22,283 probe sets present in the microarray. To assess differential expression, linked to piroxicam, cisplatin- and the combined treatment we used an empirical Bayes method together with a false discovery rate (FDR) correction of the P-value. Specifically genes were selected using a corrected p-value M-bM-^IM-$0.05 and |log2(fc)| M-bM-^IM-%1. We detect a total of 536 differentially expressed genes.
Project description:Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and drug resistance. In this study, we aimed to examine whether Jinfukang (JFK), an effective herbal medicine against lung cancer, enhances DDP-induced cytotoxicity in lung cancer cells. Morphologically, we observed JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines NCI-H1975, NCI-H1650 and NCI-H2228. Particularly, we demonstrated AIFM2 is activated by the combined treatment of JFK and DDP, and partially mediate the synergistic pro-apoptosis effect. Collectively, this study gives the first evidence that activation of AIFM2 contributes to induction of pro-apoptosis by combined treatment with JFK and DDP in human lung cancer cells and provides an insight for its potential clinical application in lung cancer treatment.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
