RESUMO
OBJECTIVE@#To compare the difference in gene expression profiles between parental cell line and drug resistant cell line (CNE-1 and CNE-1/taxol) pre-treated or treated by drugs, and search for genes related to taxol resistance and reversal of taxol resistance phenotype.@*METHODS@#cDNA microarray was used to detect the difference in gene expression profiles between 6 groups of cells. Combination of multiple filtering genes and detailed analysis of documented resistance genes were used to analyze the data.@*RESULTS@#Through multiple filtering, 297 differentially expressed genes were screened. The expression of 17 genes was increased or decreased more than 5 folds in CNE-1/taxol compared with CNE-1.Through analyzing documented drug-resistant genes, MDR1 expression was not detected in each group. CYP1A1, one of P450 family members, was not expressed in CNE-1, but significantly increased expressions was found in CNE-1/taxol and these increased expressions were restored by cisplatin. The expression level of some members of tumor necrosis factor family was decreased in CNE-1/taxol and restored by cisplatin, including TNFAIP1, 3 and TNFRSF12A, 21. The differentially expressed members in the caspase family were caspase-4 and caspase-6. The expression of β-tubulin II was down-regulated in CNE-1/taxol. TSP1 was obviously down-regulated in CNE- 1/taxol compared with CNE-1, and a more significant down-regulation of TSP1 was found when treated by taxol. However, it was greatly up-regulated after cisplatin treatment in CNE-1/taxol.@*CONCLUSION@#Some genes are probably related to taxol resistance and reversal of taxol resistance in NPC cells: 297 differentially expressed genes detected by multiple filing, CYP1A1, some members of TNF family and another 17 genes whose differential expression is more than 5 folds between parental cell line and drug resistant cell line. Combination of multiple filtering genes and detailed analysis of documented resistance genes is a good method to study drug resistance and reversal of drug resistance in carcinoma cells.
Assuntos
Humanos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Genética , Linhagem Celular Tumoral , Citocromo P-450 CYP1A1 , Genética , Resistencia a Medicamentos Antineoplásicos , Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Nasofaríngeas , Patologia , Análise de Sequência com Séries de Oligonucleotídeos , Paclitaxel , Farmacologia , Proteínas , Genética , Receptores do Fator de Necrose Tumoral , Genética , Receptor de TWEAKRESUMO
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily of structurally related cytokines and is known to induce proliferation, migration, differentiation, apoptotic cell death, inflammation, and angiogenesis. These physiological processes are induced by the binding of TWEAK to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell-surface receptor that is linked to several intracellular signaling pathways, including the nuclear factor-κB (NF-κB) pathway. This review discusses the role of the TWEAK-Fn14 axis in several rheumatic diseases and the potential therapeutic benefits of modulation of the TWEAK-Fn14 pathway.