Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Selamectin increases cisplatin sensitivity by inhibiting cisplatin-resistant genes expression and autophagy in uveal melanoma

ABSTRACT: Cisplatin resistance is the main reason for uveal melanoma (UM) treatment failure. Thus, developing strategy that increasing cisplatin sensitivity is needed. In this study, we performed drug repositioning analysis with the Connectivity Map database using a panel of previously identified cisplatin sensitivity–associated genes and cisplatin resistance–associated genes as the signature and obtained the antiparasitic drug selamectin. We demonstrated that the selamectin and cisplatin combination showed a synergistic effect on inhibiting UM cell growth. Experiments in tumor-bearing nude mice further showed that selamectin and cisplatin have synergistic effects in reducing tumor growth. Previous studies have linked increased autophagy with tumor resistance to chemotherapy. We found that selamectin inhibited the expression of the autophagy-related gene ATG9B, thus reducing autophagy. The cisplatin resistance–associated genes PDGFRB, DUSP1, MAST1 and IL11 were significantly downregulated in UM cells treated with selamectin. In summary, our study shows that selamectin enhanced the sensitivity of UM to cisplatin, through the mechanism of inhibiting cisplatin resistance–associated gene expression and autophagy. These findings may provide a new strategy for the treatment of UM.

ORGANISM(S): Homo sapiens

PROVIDER: GSE228250 | GEO | 2025/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Selamectin increases cisplatin sensitivity by inhibiting cisplatin-resistant genes expression and autophagy in uveal melanoma

Project description:Selamectin increases cisplatin sensitivity by inhibiting cisplatin-resistant genes expression and autophagy in uveal melanoma

| PRJNA949137 | ENA

The STAT3 induced ITGB4 overexpression represses p53 to reduce the sensitivity of bladder cancer to cisplatin

Project description:Cisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer, but the development of cisplatin-resistance limits its anti-tumor effects. Previous studies have shown that cisplatin resistance in bladder cancer may be related to a variety of factors, such as changes in drug transport and metabolism, enhancement of DNA repair mechanisms, changes in cell cycle regulation, inhibition of apoptosis, and epigenetic modification. While, the mechanism of cisplatin resistance is still elusive.In this study, we first found that upregulated ITGB4 is correlated with poor prognosis after chemotherapy in bladder cancer. Next, we demonstrated ITGB4 plays a key role in regulating the sensitivity of bladder cancer to cisplatin therapy. Then, we found that ITGB4 reduced the sensitivity of bladder cancer to cisplatin by inhibiting p53-S15 site phosphorylation and promoting MDM2 binding to p53 to reduce p53 expression. In addition, we demonstrated that ITGB4 regulates the antitumor effects of MDM2 inhibitors combined with cisplatin therapy. Further, we found that ITGB4 was elevated in bladder cancer cisplatin-resistant cells, and the increase in ITGB4 was mediated by STAT3.The combination of STAT3 inhibitors can enhance the antitumor effect of cisplatin in bladder cancer.In summary, we identified ITGB4 as a key molecule affecting cisplatin sensitivity in bladder cancer, and proposed a strategy of combining drugs with STAT3 inhibitors to increase cisplatin sensitivity in bladder cancer.

2024-06-07 | GSE268855 | GEO

Reciprocal epigenetic remodeling mediated by polycomb and DNMT3B control testicular cancer hypersensitivity and resistance to 5-aza and cisplatin

Project description:We undertook a pharmacogenomic approach in order to better understand mechanisms of hypomethylating agent hypersensitivity of TGCTs by generating a panel of acquired 5-aza resistant TGCT cells and contrasting these to previously generated acquired cisplatin resistance cells from the same parent. Interestingly, there was a reciprocal relationship between cisplatin and 5-aza sensitivity, with cisplatin resistance associated with increased sensitivity to 5-aza and 5-aza resistance associated with increased sensitivity to cisplatin. Unbiased transcriptome analysis revealed 5-aza resistant cells strongly downregulated polycomb target gene expression, the exact opposite of the finding for cisplatin resistant cells which upregulated polycomb target genes. This was associate with a dramatic increase in H3K27me3 and substantial decrease in DNMT3B levels in 5-aza resistant cells, the exact opposite changes seen in cisplatin resistant cells.

2021-12-31 | GSE172266 | GEO

Reciprocal epigenetic remodeling mediated by polycomb and DNMT3B control testicular cancer hypersensitivity and resistance to 5-aza and cisplatin [DNMT3B Knockdown]

2021-12-31 | GSE172458 | GEO

Cisplatin resistance driver gene CLSPN product is a target for immunotherapy in urothelial carcinoma.

Project description:Bladder cancer is a major and mortal disease in urological area. Cisplatin is a key drug for bladder cancer especially for muscle invasive cases. In most cases of bladder cancer, cisplatin is effective; however, resistance to cisplatin is critical for patient’s prognosis. Thus, treatment strategy for cisplatin resistant bladder cancer is essential to improve current prognosis. In this study, we established cisplatin resistant bladder cancer line (CR cells) using a urothelial carcinoma line UM-UC-3 cells. We screened potential targets for CR cells and found that claspin is overexpressed in CR cells. Claspin mRNA knockdown revealed that claspin has a role in cisplatin resistance in CR cells. In our previous study, we found HLA-A*02:01-restricted CLSPN peptide by an HLA ligandome analysis. We thus generated CLSPN peptide specific CTL clone and found that CLSPN peptide-specific CTL clone recognized CR cells at higher levels compared with that of UM-UC-3 wild type cells. These findings indicate that claspin is a driver for cisplatin resistance and claspin peptide-specific immunotherapy is effective for cisplatin resistant cases.

2024-04-10 | GSE217413 | GEO

Basal mRNA expression levels of single-cell derived FaDu clones with cisplatin-sensitive / resistant phenotype

Project description:The extent of intratumoral heterogeneity, the subclonal structures and the mechanisms of treatment-induced clonal selection by cisplatin was investigated in the squamous cell carcinoma cell line model FaDu. We picked 96 single cell-derived clones from the cisplatin-sensitive parental FaDu cell line. After expansion as separate cultures, these clones were tested for their sensitivity to CDDP. By this approach, we isolated individual cell clones that were primarily resistant (clones 5 & 78) and others that showed high sensitivity to CDDP (clones 46 & 54). Basal mRNA expression levels associated with CDDP sensitivity / resistance were determined in two independent microarray analyses.

2017-12-04 | E-MTAB-6022 | biostudies-arrayexpress

Expression data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines.

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.

2009-04-17 | E-GEOD-15372 | biostudies-arrayexpress

Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance

Project description:In order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identified a potential biomarker, BAG-1 (Bcl-2 associated athanogene-1), that is implicated in HNSCC insensitive to cisplatin and tumor progression. Advanced HNSCC cells revealed resistant to cisplatin accompanied by increased expression of BAG-1 protein. siRNA knockdown of BAG-1 expression resulted in significant improvement of HNSCC sensitivity to cisplatin. BAG-1 expression enhanced stability of BCL-xL and conferred cisplatin resistant to the HNSCC cells. In addition, high levels of expression of phospho AKT, BAG-1, and BCL- xL were observed in advanced HNSCC compared to in that of primary HNSCC. Conclusion: Increased expression of BAG-1 was associated with cisplatin resistance and tumor progression in HNSCC patients and warrants further validation in larger independent studies. Over expression of BAG-1 may be a biomarker for cisplatin resistance in patients with primary or recurrent HNSCCs and targeting BAG-1 could be helpful in overcoming cisplatin resistance.

2017-10-04 | GSE102787 | GEO

Tumor heterogeneity underlies differential cisplatin sensitivity in mouse models of small cell lung cancer

Project description:SCLC is the most aggressive subtype of lung cancer characterized by a remarkable response to chemotherapy followed by development of resistance. Mechanisms of initial sensitivity and of subsequent resistance are not understood. Here we highlight a broad tumor heterogeneity in mouse models of SCLC, which includes a CDH1 high primary cisplatin-resistant peripheral neuroendocrine lesion with unique metabolic and structural profile. Cisplatin treatment preferentially eliminates CDH1 negative secondary tumor leaving behind CDH1 high primary lesions, thus revealing a striking differential response. We profile global protein and messenger RNA levels in vehicle and cisplatin treated lung tumor populations and find a marked reduction in proliferation and a pronounced metabolic shift following cisplatin-treatment. Our proteo-transcriptomic analysis gives insight into gene expression alterations that characterize cisplatin resistance and uncovers potential novel targets to overcome resistance of distinct populations. SCLC tumors in the mouse show heterogeneity which appears, as might be the case in humans, to be one of the underlying mechanisms of differential sensitivity to cisplatin.

2019-11-12 | PXD010680 | Pride

Expression data from A2780 (cisplatin-sensitive) and Round5 A2780 (cisplatin-resistant) cell lines.

2009-04-17 | GSE15372 | GEO