Profiling the Panc1 pancreatic cancer cell line following Gemcitabine treatment using single cell RNA sequencing
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PROVIDER: PRJNA776896 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic ductal adenocarcinoma (PDAC) often presents at late clinical stages, and most patients are managed solely through palliative chemotherapy. With no approved treatment modalities for patients who progress on broad-spectrum chemotherapy, we set to identify druggable targets to prevent or reverse resistance to the first line anti-neoplastic Gemcitabine. In our first experiment, we used the well-established Panc1 cell line as an in vitro model of PDAC. Panc1 cells were incubated with a tolerable dose of Gemcitabine in vitro, and examined alterations in gene expression via single cell RNA sequencing. In our subsequent studies, we incubated Panc1 cells with increasing doses of Gemcitabine for several passages, until viable in approximately 10x the known IC50 value. These cells were designated Panc1-GR. Based on our observations in the prior experiment, Panc1-GR cells were compared to those treated with wither the Calmodulin inhibitor W-7, Calcium chelator BAPTA-AM, or the calcium channel blocker Amlodipine. Through these efforts, we hope to better understand the mechanisms of Gemcitabine resistance in PDAC, as well as introduce new therapeutic strategies to reverse drug resistant phenotypes in the clinic.
2022-03-21 | GSE186960 | GEO
Project description:Gemcitabine (GEM) is a key drug for treating PDAC, and it is commonly used for adjuvant chemotherapy. Although the majority of PDAC is sensitive to GEM at first, GEM cannot control PDAC for very long, suggesting that PDAC develops resistance to GEM after prolonged exposure. No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma. MicroRNAs (miR) are epigenetic gene regulators with tumorsuppressive or oncogenic roles in various carcinomas. This study assesses gemcitabine resistant PDAC for its specific miR expression pattern. Gemcitabine resistant variants of Panc1, a human pancreatic adenocarcinoma cell line, were established. MicroRNA screening was investigated by microarray.
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Project description:We reported the transcriptional effects of gemcitabine, genistein and the combined gemcitaibe/gensitein treatments on two pancreatic cancer cell lines MiaPaCa2 and PANC1. The overall purpose of the study to understand the underlying mechanism of genistein chemoenhancing function.
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Project description:We generated gemcitabine resistant subclones from the human pancreatic cancer cell line BxPC3 using chronic low dose exposure to gemcitabine. Three gemcitabine resistant subclones (BxGR-80C, BxGR-120C and BxGR-360C) were sequenced in addition to BxPC3 cells.
2021-12-21 | E-MTAB-11186 | biostudies-arrayexpress
Project description:Investigation of whole genome gene expression level changes of Panc1 pretreated with Clofibrate, compared to Panc1 pretreated with DMSO.
2015-06-09 | GSE69650 | GEO
Project description:Gemcitabine (GEM) is a key drug for treating PDAC, and it is commonly used for adjuvant chemotherapy. Although the majority of PDAC is sensitive to GEM at first, GEM cannot control PDAC for very long, suggesting that PDAC develops resistance to GEM after prolonged exposure. No reliable predictors of susceptibility to gemcitabine chemotherapy exist in pancreatic ductal adenocarcinoma. This study assesses gemcitabine resistant PDAC for its specific mRNA expression pattern. Gemcitabine resistant variants of Panc1, a human pancreatic adenocarcinoma cell line, were established. mRNA screening was investigated by microarray.
2016-04-26 | GSE80617 | GEO
Project description:Chemotherapy resistance is a major clinical issue for pancreatic adenocarcinoma (PDAC). MicroRNAs (miRNAs) play an important role in cancer progression and chemoresistance. In this study, we addressed the association between miRNA expression profiles and gemcitabine (Gem) resistance. A Gem sensitive (GS) PDAC cancer cell line, MIA PaCa-2, and its Gem resistant (GR) progeny MIA PaCa-2 GR, was used to determine miRNA expression changes by resistance to Gemcitabine. miRNA-seq was used to determine the miRNA expression profiles in these cell lines. Ingenuity Pathway Analysis (IPA) was performed to determine the biological functions of differentially expressed miRNAs. In total, 1867 miRNAs were detected in the two cell lines. We found that the miRNA expression profiles were different between the GR and its sensitive isogenic parental GS cell line, and certain differentially expressed miRNAs were only detected in one or the other of these PDAC cell lines. A total of 97 (5.2%) miRNAs were significantly differentially expressed between GR and the GS cell lines, of which 65 (3.5%) miRNAs were upregulated and 32 (1.7%) miRNAs were downregulated. The miRNAs with the most significant differential expression in the GR cell line as compared with GS were primarily involved in the following biological processes: cell proliferation, cell migration & invasion, chemo-sensitization, alternative splicing, apoptosis, and angiogenesis. These miRNAs from cell lines were further refined to a subset and were analyzed in patient samples where expression was used to identify patients with recurrent tumors. Taken together, the results suggest that these miRNAs may play important roles in Gem resistance in PDAC. This study’s findings provides a basis for further research in the diagnosis and treatment selection for PDACs with gemcitabine resistance.
2024-07-01 | GSE269190 | GEO
Project description:Purpose: Chemotherapy is pivotal in the multimodal treatment of pancreatic cancer patients. In recent years, technical advances have developed experimental methods that unveiled a high degree of inter- and intratumoral heterogeneity in pancreatic cancer. We hypothesized that intratumoral heterogeneity (ITH) impacts response to gemcitabine treatment and demands specific targeting of resistant subclones. Experimental Design: We addressed the effect of ITH on response to gemcitabine treatment using single cell-derived cell lines (SCDCL) from the classical-like cell line BxPC3 and the basal-like cell line Panc-1 which were analyzed by mRNA-seq and mass spectrometry. Results: Individual SCDCLs of the parental tumor cell populations of BxPC3 and Panc-1 showed considerable heterogeneity in response to gemcitabine. Unsupervised principal component analysis (PCA) including the 1,000 most variably expressed genes showed a clustering of the SCDCLs according to their respective sensitivity to gemcitabine treatment for BxPC3, while this clustering was less clear for Panc-1. In BxPC3 SCDCLs, enriched signaling pathways EMT, TNF signaling via NfKB, and IL2STAT5 signaling correlated with more resistant behavior to gemcitabine. In Panc-1 SCDCLs MYC targets V1 and V2 as well as E2F targets were associated with stronger resistance to gemcitabine. Feature extraction of proteomes again identified less proteins whose expression was associated with the response of individual SCDCLs in Panc-1 compared to BxPC3. Based on molecular profiles, we could show that the gemcitabine-resistant SCDCLs of both BxPC3 and Panc-1 are more sensitive to the BET inhibitor JQ1 compared to the respective gemcitabine-sensitive SCDCLs. Conclusions: Our model system of SCDCLs identified gemcitabine-resistant subclones within a parental tumor population and provides evidence for the critical role of ITH for treatment response in pancreatic cancer. Through molecular profiling, we identified specific signaling pathways and protein signatures that might help to explain the differential response to treatment among clones. We exploited these molecular differences for an improved and more targeted therapy of resistant subclones of a heterogeneous tumor.
2023-09-19 | PXD042256 | Pride