Key players of cisplatin resistance: towards a systems pharmacology approach
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ABSTRACT:
PROVIDER: PRJNA422859 | ENA |
REPOSITORIES: ENA
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Project description:The cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549rCDDP2000 was screened with a whole genome array for gene candidates relevant for cisplatin resistance.
2018-04-17 | GSE108214 | GEO
Project description:The major obstacle in the clinical use of the antitumor drug cisplatin is inherent and acquired resistance. Typically, cisplatin resistance is not restricted to a single mechanism demanding for a systems pharmacology approach to understand a whole cell's reaction to the drug. In this study, the cellular transcriptome of untreated and cisplatin-treated A549 non-small cell lung cancer cells and their cisplatin-resistant sub-line A549rCDDP2000 was screened with a whole genome array for relevant gene candidates. By combining statistical methods with available gene annotations and without a previously defined hypothesis HRas, MAPK14 (p38), CCL2, DOK1 and PTK2B were identified as genes possibly relevant for cisplatin resistance. These and related genes were further validated on transcriptome (qRT-PCR) and proteome (Western blot) level to select candidates contributing to resistance. HRas, p38, CCL2, DOK1, PTK2B and JNK3 were integrated into a model of resistance-associated signalling alterations describing differential gene and protein expression between cisplatin-sensitive and -resistant cells in reaction to cisplatin exposure.
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Project description:Platinum resistance is a major drawback in the treatment of ovarian cancer. Evidence suggests that microRNAs are key players in the initiation, progression, and drug resistance of cancer cells. However, the precise miRNAs dysregulated and contributing to platinum resistance in ovarian cancer cells have not been fully elucidated. Here, we conducted a miRNA expression profiling of cisplatin-sensitive (A2780) and cisplatin-resistant (CP20 and CIS) ovarian cancer cells to identify potential miRNAs involved in platinum resistance.
2020-11-20 | GSE161784 | GEO
Project description:NF-E2-related factor 2 (Nrf2), a transcription factor activated by oxidative stress, induces phase II conjugating or antioxidant enzymes. In the present study, we examined the effect of Nrf2 knockout (Nrf2 KO) on the kidney injury induced by cisplatin using cDNA microarray analyses. A transcriptomic approach enabled us to extract gene clusters which show significantly different mRNA expression patterns between wild type (WT) and Nrf2 KO mice. In the experimental set, WT vehicle (WT-Veh) and WT cisplatin (WT-Cis) groups were included in our previous GEO database (GSE35257) because the two groups were simultaneously shared with Nrf2 KO vehicle (Nrf2 KO-Veh) and Nrf2 KO cisplatin (Nrf2 KO-Cis) groups in the current report. Copyright (c) 2012 by Korea Food & Drug Administration. WT and Nrf2 KO C57BL/6 mice (9 weeks old, male) were intraperitoneally injected with vehicle (saline) or a single dose of cisplatin (15 mg/kg body weight). The cDNA microarray experiments were done for the kidney of mice 3 days after treatment. Three animals were used per group. WT-Veh and WT-Cis groups were already deposited in GSE35257.
2014-01-01 | E-GEOD-48879 | biostudies-arrayexpress
Project description:Cisplatin, a platinating agent commonly used in treating several cancers is associated with nephrotoxicity, neurotoxicity and ototoxicity that have hindered its utility. To gain a better understanding of the genetic variants associated with cisplatin induced toxicity, we present a step-wise approach integrating genotypes, gene expression and sensitivity of HapMap cell lines to cisplatin. Cell lines derived from 30 trios of European descent (CEU) and 30 trios of African descent (YRI) were utilized to develop a preclinical model to identify genetic variants and gene expression that contribute to cisplatin induced cytotoxicity in two different populations. Cytotoxicity was determined as cell growth inhibition at increasing concentrations of cisplatin for 48 h. Gene expression on 176 HapMap cell lines (87 CEU and 89 YRI) was determined using the Affymetrix GeneChip® Human Exon 1.0 ST Array. We identified 6, 2 and 9 representative SNPs that contribute to cisplatin-induced cytotoxicity through their effects on 8, 2 and 16 gene expressions in the combined, CEPH and Yoruban populations, respectively. These genetic variants contribute to 27, 29 and 45% of the overall variation in cell sensitivity to cisplatin in the combined, CEPH and Yoruban populations, respectively. Our whole genome approach can be used to elucidate expression quantitative trait loci contributing to a wide range of cellular phenotypes. Keywords: exon array
2007-06-06 | GSE7761 | GEO
Project description:NF-E2-related factor 2 (Nrf2), a transcription factor activated by oxidative stress, induces phase II conjugating or antioxidant enzymes. In the present study, we examined the effect of Nrf2 knockout (Nrf2 KO) on the kidney injury induced by cisplatin using cDNA microarray analyses. A transcriptomic approach enabled us to extract gene clusters which show significantly different mRNA expression patterns between wild type (WT) and Nrf2 KO mice. In the experimental set, WT vehicle (WT-Veh) and WT cisplatin (WT-Cis) groups were included in our previous GEO database (GSE35257) because the two groups were simultaneously shared with Nrf2 KO vehicle (Nrf2 KO-Veh) and Nrf2 KO cisplatin (Nrf2 KO-Cis) groups in the current report. Copyright (c) 2012 by Korea Food & Drug Administration.
2014-01-01 | GSE48879 | GEO
Project description:To investigate the mode of action of ccc_R08, a first-in-class orally available HBV cccDNA inhibitor, we designed and implemented two orthogonal and complementary approaches: a forward pharmacology approach and a reverse pharmacology approach. Bioinformatics analysis integrating biological knowledge with the observations from both approaches offered us preliminary insights into the mode of action of ccc_R08.
2022-12-30 | GSE214515 | GEO
Project description:A2780 ovarian cancer cells and a cisplatin resistant derivate of A2780 cells, obtained from ECACC, UK, No. 93112519 [A2780] and No. 93112517 [A2780 cis] were seeded out in T-75 flasks at a density of 2x106 for A2780sens and 3x106 for A2780cis cells in 15 ml of medium and preincubated overnight. Medium was removed and 15 ml fresh medium (37M-0C) with different concentrations of cisplatin, liposomal cisplatin or empty liposomes were added and incubated for 72 h at 37M-0C in a 5% CO2 incubator. In case of A2780sens cells, 1.72 M-5M cisplatin (IC50 concentration) and in case of A2780cis cells 8.94 M-5M cisplatin (IC50 concentration) were added. Liposomal formulations contained equal cisplatin concentrations. Empty liposomes were added in the same concentration as the liposomal cisplatin, to analyze the impact of liposomal lipids (A2780sens: 0.80M-5mol lipid, A2780cis: 4.15 M-5mol lipid). After incubation, medium was removed and cells were washed thrice with 10 ml PBS. 1 ml RLT-buffer was added and cells lysates were stored at -80M-0C until RNA extraction.
2010-12-13 | E-MEXP-2840 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE15372: Expression data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. GSE15373: Promoter CpG island methylation data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines. Refer to individual Series
2009-04-17 | E-GEOD-15709 | biostudies-arrayexpress
Project description:Chemotherapy is still the standard–of-care for triple-negative breast cancers (TNBCs). Here, we investigated miR-302b as therapeutic tool to enhance cisplatin sensitivity in vivo and unraveled the molecular mechanism. Material and method: TNBC xenografted mice were treated with miR-302b or control, alone or with cisplatin. Genome-wide transcriptome analysis and independent-validation of ITGA6 expression was assessed on mice tumor samples. SiRNA-knockdown of ITGA6 was performed to evaluate cisplatin response in vitro. Further, potential transcription factors of ITGA6 (E2F1, E2F2 and YY1) were explored to define the miRNA molecular mechanism. MiR-302b expression was also assessed in TNBC patients treated with chemotherapy. Results: MiR-302b-cisplatin combination significantly impaired tumor growth versus control, through indirect ITGA6 downregulation. Indeed, ITGA6 was downmodulated in mice treated with miR-302b-cisplatin and ITGA6 silencing increased drug sensitivity in TNBC cells. In silico analyses and preclinical assays pointed out the regulatory role of E2F family and YY1 on ITGA6 expression under miR-302b-cisplatin treatment. Finally, miR-302b enrichment correlates with better overall survival in 118 TNBC patients. Conclusion: MiR-302b can be exploited as a new therapeutic tool to improve the response to chemotherapy, modulating E2F family, YY1 and ITGA6 expression. Moreover, miR-302b could be defined as new prognostic factor in TNBC patients.
2020-08-21 | GSE152322 | GEO