Similar Datasets
Project description:Platinum compounds display clinical activity against a wide variety of solid tumors. However, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux-kinetics indicated that ATP11B enhances the export of cisplatin from cells. The co-localization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins such as syntaxin-6 (STX6) and vesicular associated membrane protein 4 (VAMP4) strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, silencing ATP11B expression might be a therapeutic strategy to overcome cisplatin resistance. We performed the transfection of control-siRNA and ATP11B-siRNA to both cisplatin-sensitive A2780-PAR and cisplatin-resistant A2780-CP20 cells respectively.
2013-01-23 | E-GEOD-43694 | biostudies-arrayexpress
Project description:DDX18 enhances platinum resistance in ovarian cancer
| PRJNA1380341 | ENA
Project description:circASCOR enhances platinum resistance in ovarian cancer
| PRJNA1398198 | ENA
Project description:Platinum compounds display clinical activity against a wide variety of solid tumors. However, resistance to these agents is a major limitation in cancer therapy. Reduced platinum uptake and increased platinum export are examples of resistance mechanisms that limit the extent of DNA damage. Here, we report the discovery and characterization of the role of ATP11B, a P-type ATPase membrane protein, in cisplatin resistance. ATP11B gene silencing restored the sensitivity of ovarian cancer cell lines to cisplatin in vitro. Combined therapy of cisplatin and ATP11B-siRNA significantly decreased cancer growth in mice bearing ovarian tumors derived from cisplatin-sensitive and -resistant cells. In vitro mechanistic studies on cellular platinum content and cisplatin efflux-kinetics indicated that ATP11B enhances the export of cisplatin from cells. The co-localization of ATP11B with fluorescent cisplatin and with vesicular trafficking proteins such as syntaxin-6 (STX6) and vesicular associated membrane protein 4 (VAMP4) strongly suggests that ATP11B contributes to secretory vesicular transport of cisplatin from Golgi to plasma membrane. In conclusion, silencing ATP11B expression might be a therapeutic strategy to overcome cisplatin resistance.
2013-01-23 | GSE43694 | GEO
Project description:We treated 8 human ovarian cancer cell lines with cisplatin in treatment/recovery cycles to induce in-vitro resistance to the drug. Microarrays measured gene expression at baseline and after each dose schedule (after recovery).
2011-10-03 | GSE23553 | GEO
Project description:We treated 8 human ovarian cancer cell lines with cisplatin in treatment/recovery cycles to induce in-vitro resistance to the drug. Microarrays measured gene expression at baseline and after each dose schedule (after recovery). OVCA cells lines (T8, OVCAR5, OV2008, IGROV1, C13, A2780S, A2780CP, and A2008) were used in the study. Cells were subject to sequential treatment with increasing doses of cis-diammine-dichloroplatinum (cisplatin, CIS), using three dosing schedules resulting in a total of 144 treatment/expansion cycles. Treatment schedules A, B and C included three treatments with 1, 2 and 3μg/ml CIS respectively, followed by three treatments with 3, 4 and 5μg/ml, respectively. Each CIS-treatment was followed by a cell recovery/expansion phase. Both CIS-resistance and genome-wide expression changes were measured serially in each cell line at baseline and after 3 and 6 CIS-treatment/expansion cycles. CIS-resistance was quantified using CellTiter-96, MTS proliferation assays (Fisher Scientific) and genome-wide expression was performed using Affymetrix Human U133 Plus 2.0 GeneChips as previously described.
2011-10-02 | E-GEOD-23553 | biostudies-arrayexpress
Project description:To investigate functional lncRNAs in ovarian cancer ascites exosomes, we performed high-throughput RNA sequencing (RNA-seq) of ascites-derived exosomes from 3 cisplatin-sensitive and 7 cisplatin-resistant HGSOC patients
2023-11-15 | GSE247337 | GEO
Project description:Seventy percent of women with ovarian cancer develop resistance to cisplatin, contributing to persistently high mortality rates. Understanding the mechanisms behind this resistance is crucial for developing improved therapies. Matrix metalloproteinase 3 (MMP3) is elevated in ovarian cancer patients, but its role in cisplatin resistance remains underexplored. We observed significantly higher MMP3 protein and mRNA levels in cisplatin-resistant high-grade serous ovarian cancer (HGSOC) cells compared to cisplatin-sensitive cells, with further increases following cisplatin treatment. Kaplan‒Meier analysis indicated that patients with lower MMP3 levels have better survival outcomes. MMP3 knockdown via siRNA reduced cell viability, proliferation, and invasion, effects enhanced by cisplatin; however, a chemical MMP3 inhibitor did not replicate these effects. To better understand MMP3’s role, we conducted RNA sequencing to analyze gene expression changes and used immunoprecipitation with mass spectrometry to identify MMP3-interacting proteins, making this the first study to explore this in cisplatin-resistant ovarian cancer. Surprisingly, multiple injections of liposomal MMP3-siRNA increased tumor size in a mouse model, while combining MMP3-siRNA with cisplatin reduced tumor growth. These findings highlight MMP3’s complex role in cisplatin resistance and raise concerns about its targeting in vivo.
2025-04-24 | GSE275051 | GEO
Project description:Characterization of differential gene expression due to cisplatin resistance in human ovarian cancer spheroids by microarray analysis. In this dataset, we include the expression data obtained from cisplatin-sensitive and cisplatin-resistant human ovarian cancer spheroids. These data are used to obtain 1316 genes that are differentially expressed in response to cisplatin resistance.
2015-12-01 | GSE45553 | GEO
Project description:Ovarian cancer is a highly malignant gynecological tumor. Multidrug resistance (MDR) in tumors is a major reason for chemotherapy failure. Keratin 14 (KRT14), a member of the keratin family, plays a significant role across various cancers. Elevated KRT14 expression has been observed in ovarian cancer tissues compared to normal ovarian tissues, and this differential expression is associated with poorer progression-free survival in patients undergoing platinum and taxol-based chemotherapy. Furthermore, KRT14 expression is heightened in migratory ovarian cancer cells, where it plays a crucial role at the invasive interface, facilitating ovarian cancer cell invasion. The role of KRT14 in regulating MDR is not known. In this study, we aimed to investigate the effects and mechanisms of KRT14 in human cisplatin-resistant ovarian cancer cell lines SK-OV-3/DDP and A2780/DDP.
2025-04-17 | GSE276216 | GEO