Gene expression associated with acquired paclitaxel resistance in ovarian cancer cell lines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA721703 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14231503.fastq.gz | Fastqsanger.gz | |||
| SRR14231504.fastq.gz | Fastqsanger.gz | |||
| SRR14231505.fastq.gz | Fastqsanger.gz | |||
| SRR14231506.fastq.gz | Fastqsanger.gz | |||
| SRR14231507.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 26 |
Similar Datasets
Project description:Conventional frontline treatment for ovarian cancer consists of successive chemotherapy cycles of paclitaxel and platinum. Despite the initial favorable responses for most patients, chemotherapy resistance frequently leads to recurrent or refractory disease. New treatment strategies that circumvent or prevent mechanisms of resistance are needed to improve ovarian cancer therapy. We developed in vitro ovarian cancer cell line models of acquired paclitaxel resistance using 2 immortalized human ovarian cancer cell lines, OVCAR3 and TOV-21G. We also developed in vitro primary ovarian cancer organoid models using tumor tissue from 7 patients with gynecologic malignancies. Gene expression differences in resistant and sensitive lines were analyzed by RNA sequencing to identify potential mechanisms of paclitaxel resistance in primary ovarian cancer.
2021-07-02 | GSE172016 | GEO
Project description:The microtubule-stabilising drug paclitaxel has activity in relapsed ovarian cancer. However, resistance frequently develops. Oncolytic adenoviruses are a novel cancer therapy, and replicate selectively within and lyse malignant cells, leading to productive infection of neighbouring cells. We found increased efficacy of adenoviruses of multiple subtypes in paclitaxel-resistant ovarian cancer cells. There was increased expression of a key adenovirus receptor, CAR (coxsackie adenovirus receptor), due to increased transcription that resulted from histone modification. Moreover, CAR transcription increased in intraperitoneal xenografts with acquired paclitaxel resistance and in tumours from patients with paclitaxel-resistant ovarian cancer. Finally, we identified dysregulated cell cycle control as a second mechanism of increased adenovirus efficacy in paclitaxel-resistant ovarian cancer and that inhibition of CDK4/6 using PD-0332991 was able both to reverse paclitaxel resistance and reduce adenovirus efficacy. Thus, paclitaxel resistance increases oncolytic adenovirus efficacy via at least two separate mechanisms. Parental SKOV3 and paclitaxel-resistant SKOV3-TR cells were analysed in duplicate
2015-12-10 | E-GEOD-54772 | biostudies-arrayexpress
Project description:Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. 21 ovarian cancer cell lines treated with eribulin and paclitaxel for 24 hours at concentration 10xIC50. Three technical replicates were included for eribulin , paclitaxel and untreated cell lines.
2014-10-02 | E-GEOD-50831 | biostudies-arrayexpress
Project description:The microtubule-stabilising drug paclitaxel has activity in relapsed ovarian cancer. However, resistance frequently develops. Oncolytic adenoviruses are a novel cancer therapy, and replicate selectively within and lyse malignant cells, leading to productive infection of neighbouring cells. We found increased efficacy of adenoviruses of multiple subtypes in paclitaxel-resistant ovarian cancer cells. There was increased expression of a key adenovirus receptor, CAR (coxsackie adenovirus receptor), due to increased transcription that resulted from histone modification. Moreover, CAR transcription increased in intraperitoneal xenografts with acquired paclitaxel resistance and in tumours from patients with paclitaxel-resistant ovarian cancer. Finally, we identified dysregulated cell cycle control as a second mechanism of increased adenovirus efficacy in paclitaxel-resistant ovarian cancer and that inhibition of CDK4/6 using PD-0332991 was able both to reverse paclitaxel resistance and reduce adenovirus efficacy. Thus, paclitaxel resistance increases oncolytic adenovirus efficacy via at least two separate mechanisms.
2015-12-10 | GSE54772 | GEO
Project description:Paclitaxel is a first-line drug for treating epithelial ovarian cancer (EOC). However, prognosis for patients with advanced stage cancer remains poor due to primary or acquired drug resistance. Therefore, overcoming chemoresistance is one of the greatest challenges in treating EOC. In this study, we identified microRNAs (miRNA) that regulate paclitaxel resistance and tested their potential utility as therapeutic targets. Paclitaxel-resistant cell lines were established using two EOC cell lines: SKVO3ip1 and HeyA8. miRNA PCR arrays showed that miR-194-5p was downregulated in paclitaxel-resistant cells. Forced expression of miR-194-5p resensitized resistant cells to paclitaxel. Conversely, miR-194-5p inhibition induced paclitaxel resistance in parental cells. In silico analysis and luciferase reporter assay revealed that MDM2 is a direct target of miR-194-5p. MDM2 was upregulated in paclitaxel resistant cells compared with parental cells. MDM2 inhibition also resensitized resistant cells to paclitaxel and forced MDM2 induced paclitaxel resistance in parental cells. miR-194-5p induced p21 upregulation and G1 phase arrest in resistant cells by downregulating MDM2. Furthermore, a public database showed that high MDM2 expression was associated with a shorter progression-free survival in EOC patients treated with paclitaxel. Collectively, our results show that restoring miR-194-5p expression resensitizes EOCs to paclitaxel, and this may be exploited as a therapeutic option.
2019-10-18 | GSE139043 | GEO
Project description:Resistance to anti-cancer drugs is the main challenge in oncology. In pre-clinical studies established cancer cell lines are primary tools in deciphering molecular mechanisms of this phenomenon. In this study we proposed a new approach, based on a model of isogenic cancer cell lines with gradually changing resistance. We analyzed trends in gene expression to find out a scaffold of resistance development process. Ovarian cancer cell line A2780 was treated with stepwise increased concentrations of paclitaxel (PTX) to generate a series of drug resistant sublines. To monitor transcriptome changes we submitted them to mRNA-sequencing, followed by identification of differentially expressed genes (DEGs), principal component analysis (PCA) and hierarchical clustering. Functional interactions of proteins, encoded by DEGs, were analyzed by building protein-protein interaction (PPI) networks. We provided a model of human ovarian cancer cell lines with gradually developed resistance to PTX and collateral sensitivity to cisplatin (CDDP) (inverse resistance). In their transcriptomes we identified two groups of DEGs: 1) with fluctuations in expression in the course of resistance acquiring; and 2) with consistently changed expression in each stage of resistance development, constituting a scaffold of the process. In the scaffold PPI network, cell cycle regulator – PLK2; proteins belong to TNF ligand and receptor family as well as ephrin receptor family were found, but proteins linked to osteo- and chondrogenesis and nervous system development turned out to be key players. Our cellular model of drug resistance allowed for keeping track of trends in gene expression and studying this phenomenon as a process of evolution. This approach revealed that abrogation of osteomimic phenotype in ovarian cancer cells may occur during the development of inverse resistance to PTX and CDDP.
2020-12-15 | GSE159791 | GEO
Project description:Gene expression deregulation in ovarian cancer cells with acquired inverse resistance to paclitaxel and cisplatin
| PRJNA670476 | ENA
Project description:Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. 27 breast cancer cell lines treated with eribulin and paclitaxel for 24 hours at concentration 10xIC50. Three technical replicates were included. for eribulin , paclitaxel and untreated cell lines.
2014-10-02 | E-GEOD-50811 | biostudies-arrayexpress
Project description:Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics, leading to inhibition of microtubule growth in the absence of effects on microtubule shortening at microtubule plus ends, and formation of nonproductive tubulin aggregates. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. 19 endometrial cancer cell lines treated with eribulin and paclitaxel for 24 hours at concentration 10xIC50. Three technical replicates were included. for eribulin , paclitaxel and untreated cell lines.
2014-10-02 | E-GEOD-50830 | biostudies-arrayexpress
Project description:MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared to that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and real-time RT-PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays. Total RNA obtained from four different chemo-resistant subcell lines (skp 41,43,44,46) compared to parent cell line (skov3), human ovary cacinoma
2013-01-17 | E-GEOD-43598 | biostudies-arrayexpress