Project description:Drug resistance poses a major challenge to ovarian cancer treatment. Understanding mechanisms of drug resistance is important for finding new therapeutic targets. In the present work, a cisplatin-resistant ovarian cancer cell line A2780-DR was established with a resistance index of 6.64. The cellular accumulation of cisplatin was significantly reduced in A2780-DR cells as compared to A2780 cells consistent with the general character of drug resistance. Quantitative proteomic analysis identified 340 differentially expressed proteins between A2780 and A2780-DR cells, which involve in diverse cellular processes, including metabolic process, cellular component biogenesis, cellular processes and stress responses. Expression levels of Ras-related proteins Rab 5C and Rab 11B in A2780-DR cells were lower than those in A2780 cells as confirmed by real-time quantitative PCR and western blotting. The short hairpin (sh)RNA-mediated knockdown of Rab 5C in A2780 cells resulted in markedly increased resistance to cisplatin whereas overexpression of Rab 5C in A2780-DR cells increases sensitivity to cisplatin, demonstrating that Rab 5C-dependent endocytosis plays an important role in cisplatin resistance. Our results also showed that expressions of glycolytic enzymes PKM, GPI, Aldolase, LDH, and PGK were down-regulated in drug resistant cells, indicating drug resistance in ovarian cancer is directly associated with a decrease in glycolysis. Furthermore, it was found that glutathione reductase were up-regulated in A2780-DR, while vimentin, HSP90, and Annexin A1 and A2 were down-regulated. Taken together, our results suggest that drug resistance in ovarian cancer cell line A2780 is caused by multifactorial traits, including the down-regulation of Rab 5C-dependent endocytosis of cisplatin, glycolytic enzymes and vimentin, and up-regulation of antioxidant proteins, suggesting Rab 5C is a potential target for treatment of drug-resistant ovarian cancer. This constitutes a further step towards a comprehensive understanding of drug resistance in ovarian cancer.
Project description:We compared the global RNA expression level between doxorubicin-sensitive human ovarian cancer cell line A2780 and the adriamycin-resistant cell line A2780-ADR to elucidate the drug resistant related molecular mechanisms or targets.
Project description:To determine the signaling networks that are dysregulated in platinum-resistant ovarian cancer, gene expression data were obtained from, and compared between, the ovarian cancer cell line, A2780, and its cisplatin-resistant derivative, A2780cis. Gene expression data from a cisplatin-sensitive ovarian cancer cell line (A2780) were collected and compared to gene expression data from a cisplatin-resistant cell line (A2780cis). 6 independent experiments were completed for both the sensitive and resistant cell lines.
Project description:Purpose: To study differential mRNA and precursor miRNA expression under hypoxia exposure in cancer cells. We treated ovarian cancer cell line A2780 under hypoxia condition at different time points. Normoxi acultured cells at corresponding time point were used as controls.
Project description:A2780 is a cisplatin sensitive ovarian cancer cell line. A2780 ovarian cancer cells was treated with different doses of cisplatin in an attempt to identify biomarkers that can be used to predict chemoresponse. We used microarrays to identify genes induced by cisplatin in a time dependent manner.
Project description:Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, subsequently resulting in a poor long-term prognosis. To model the onset of drug resistance, we measured gene expression alterations associated with cisplatin resistance. We treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After 5 cycles of drug selection, the isogenic drug-sensitive (parental A2780) and -resistant (Round5 A2780) cell lines were subjected to mRNA expression microarray analyses.
Project description:Transcriptional profiling of human ovarian cancer cells comparing control vehicle-treated A2780 and OVCAR-3 (Human ovarian cancer cell lines) cells with A2780 and OVCAR-3 cells treated with 5μM LS-98 for 24 hours.Goal was to determine the effects of LS-98 compound on the global A2780 and OVCAR-3 cells gene expression.