Summary of Study ST003694
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002249. The data can be accessed directly via it's Project DOI: 10.21228/M8XC02 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003694 |
| Study Title | FOLFIRINOX effects on lipidomics in pancreatic cancer cells |
| Study Summary | To understand the effects of FOLFIRINOX treatment on lipid metabolism in PDAC cells, MiaPaCa2 cells were treated with the mFOLFIRINOX cocktail consisted of 5-FU, SN-38 (metabolic product of Irenocan responsible for its inhibitory activity toward DNA topoisomerase I) and oxaliplatin at 10 uM, 5uM and 10 uM, respectively, for 24 hours. The lipids were extracted, and targeted metabolomics screening were carried out to determine the effects of lomitapide treatment. |
| Institute | Pennsylvania State University |
| Last Name | Yang |
| First Name | Shengyu |
| Address | 500 University Drive |
| sxy99@psu.edu | |
| Phone | 7175311721 |
| Submit Date | 2024-12-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-09-29 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002249 |
| Project DOI: | doi: 10.21228/M8XC02 |
| Project Title: | Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma (PDAC). |
| Project Summary: | Cystine/cysteine is critical for antioxidant response and sulfur metabolism in cancer cells and is one of the most depleted amino acids in the PDAC microenvironment. The effects of cystine limitation stress (CLS) on PDAC progression are poorly understood. Here we report that adaptation to CLS (CLSA) promotes PDAC cell proliferation and tumor growth through translational upregulation of the oxidative pentose phosphate pathway (OxPPP). OxPPP activates the de novo synthesis of nucleotides and fatty acids to support tumor growth. On the other hand, CLSA-mediated lipidomic reprogramming depends on triacylglycerides synthesis to mitigate lipotoxicity. Through drug screening, we identified lomitapide as an inhibitor of CLSA PDAC tumor growth and a potent sensitizer of FOLFIRINOX chemotherapy. Mechanistically, lomitapide inhibits triacylglycerides synthesis to interfere with CLSA and chemotherapy-induced lipidomic reprograming. Taken together, CLSA-mediated metabolic and lipidomics reprograming promotes PDAC tumor growth and lomitapide could be used to target the dysregulated lipid metabolism in PDAC. |
| Institute: | Pennsylvania State University |
| Last Name: | Yang |
| First Name: | Shengyu |
| Address: | 500 University Drive |
| Email: | sxy99@psu.edu |
| Phone: | 7175311721 |
Subject:
| Subject ID: | SU003826 |
| Subject Type: | Cultured cells |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA403900 | F-1 | FOLFIRINOX |
| SA403901 | F-2 | FOLFIRINOX |
| SA403902 | F-3 | FOLFIRINOX |
| SA403903 | con-1 | vehicle |
| SA403904 | con-2 | vehicle |
| SA403905 | con-3 | vehicle |
| Showing results 1 to 6 of 6 |
Collection:
| Collection ID: | CO003819 |
| Collection Summary: | 1x107 cells were harvested using a cell scrapper. The cell pellets were resuspended in 100 μL dH2O containing proteinase inhibitors. 50 μL cell suspensions were used for lipid extraction while the remaining samples were used for protein assay. |
| Sample Type: | pancreatic cancer cells |
Treatment:
| Treatment ID: | TR003835 |
| Treatment Summary: | Cells were treated with vehicle control or the mFOLFIRINOX cocktail consisted of 5-FU, SN-38 and oxaliplatin at 10 μM, 5 μM and 10 μM, respectively, for 24 hours. The lipids were extracted, and targeted metabolomics screening were carried out to determine the effects of lomitapide treatment. |
Sample Preparation:
| Sampleprep ID: | SP003833 |
| Sampleprep Summary: | 1x107 cells were harvested using a cell scrapper. The cell pellets were resuspended in 100 μL dH2O containing proteinase inhibitors. 50 μL cell suspensions were used for lipid extraction while the remaining samples were used for protein assay. |
Chromatography:
| Chromatography ID: | CH004605 |
| Instrument Name: | Ultra Performance Liquid Chromatography (UPLC) (Nexera LC-40) |
| Column Name: | Thermo Accucore™C30 (100 x 2.1 mm, 2.6 μm) |
| Column Temperature: | 45°C |
| Flow Gradient: | Gradient program: 80:20(V/V) at 0 min, 70:30(V/V) at 2 min, 40:60(V/V) at 4 min , 15:85(V/V) at 9 min, 10:90(V/V) at 14 min, 5:95(V/V) at 15.5 min, 5:95(V/V) at 17.3 min, 80:20(V/V) at 17.5 min, 80:20(V/V) at 20 min; |
| Flow Rate: | 0.35 mL/min; |
| Solvent A: | 60% Acetonitrile/40% Water; 0.1% formic acid, 10 mmol/L ammonium formate |
| Solvent B: | 10% Acetonitrile/90% Isopropyl alcohol; 0.1% formic acid, 10 mmol/L ammonium formate |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006060 |
| Laboratory Name: | Metware Bio |
| Analysis Type: | MS |
| Chromatography ID: | CH004605 |
| Num Factors: | 2 |
| Num Metabolites: | 602 |
| Units: | pmol/mg protein |
| Analysis ID: | AN006061 |
| Laboratory Name: | Metware Bio |
| Analysis Type: | MS |
| Chromatography ID: | CH004605 |
| Num Factors: | 2 |
| Num Metabolites: | 551 |
| Units: | pmol/mg protein |
