摘要
AIM To explore novel therapeutic target of cisplatin resistance in human gastric cancer.METHODS The sensitivity of SGC7901 cells and cisplatin-resistant SGC7901 cells(SGC7901/DDP) for cisplatin were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. High-quality total RNA which isolated from SGC7901/DDP cells and SGC7901 cells were used for mR NA microarray analysis. Results were analyzed bioinformatically to predict their roles in the development of cisplatin resistance and the expression of 13 dysregulated mR NAs we selected were validated by quantitative real-time polymerase chain reaction(qR T-PCR). RESULTS SGC7901/DDP cells highly resistant to cisplatin demonstrated by MTT assay. A total of 1308 m RNAs(578 upregulated and 730 downregulated) were differentially expressed(fold change ≥ 2 and P-value < 0.05) in the SGC7901/DDP cells compared with SGC7901 cells. The expression of mR NAs detected by q RT-PCR were consistent with the microarray results. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis demonstrated that the differentially expressed mR NAs were enriched in PI3K-Akt, Notch, MAPK, ErbB, Jak-STAT, NF-kappa B signaling pathways which may be involved in cisplatin resistance. Several genes such as PDE3 B, VEGFC, IGFBP3, TLR4, HIPK2 and EGF may associated with drug resistance of gastric cancer cells to cisplatin.CONCLUSION Exploration of those altered mR NAs may provide more promising strategy in diagnosis and therapy for gastric cancer with cisplatin resistance.
AIM To explore novel therapeutic target of cisplatin resistance in human gastric cancer. METHODS The sensitivity of SGC7901 cells and cisplatin-resistant SGC7901 cells (SGC7901/DDP) for cisplatin were detected by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay. High-quality total RNA which isolated from SGC7901/DDP cells and SGC7901 cells were used for mRNA microarray analysis. Results were analyzed bioinformatically to predict their roles in the development of cisplatin resistance and the expression of 13 dysregulated mRNAs we selected were validated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS SGC7901/DDP cells highly resistant to cisplatin demonstrated by MTT assay. A total of 1308 mRNAs ( 578 upregulated and 730 downregulated) were differentially expressed ( fold change >= 2 and P-value < 0.05) in the SGC7901/DDP cells compared with SGC7901 cells. The expression of mRNAs detected by qRT-PCR were consistent with the microarray results. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction analysis demonstrated that the differentially expressed mRNAs were enriched in PI3K-Akt, Notch, MAPK, ErbB, Jak-STAT, NF-kappaB signaling pathways which may be involved in cisplatin resistance. Several genes such as PDE3B, VEGFC, IGFBP3, TLR4, HIPK2 and EGF may associated with drug resistance of gastric cancer cells to cisplatin. CONCLUSION Exploration of those altered mRNAs may provide more promising strategy in diagnosis and therapy for gastric cancer with cisplatin resistance.
基金
Supported by Projects of Foreign Science and Technology Cooperation of Anhui Province of Anhui Province,No.1604b0602027
New Century Excellent Talents in University,Ministry of Education of China,No.NCET-13-0644
Wanjiang Scholars Program of Anhui Province of China
