Summary of Study ST002703

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 PR001674. The data can be accessed directly via it's Project DOI: 10.21228/M8B14V 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	ST002703
Study Title	Multi-Omics Analysis Revealed a Significant Molecular Changes in Doxorubicin-Resistant Lung Cancer Cells.
Study Type	LC/MS/MS
Study Summary	Lung cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy resistance in lung cancer is one of the major characteristics of an aggressive phenotype with poor prognosis. Therefore, there is a critical need to explore the significant molecular changes associated with resistance to conventional chemotherapy, and identify potential therapeutic targets for treatment of resistant lung cancer. In this study, we have performed comprehensive quantitative proteomics and metabolomics analysis of non-small cell lung cancer cells (A549-P) and doxorubicin resistant A549 cells (A549-R), using state-of-the-art Trapped Ion Mobility Spectroscopy, Time-of-Flight Mass Spectrometry (TIMS-TOF-MS). The results revealed 30 dysregulated proteins and 37 significantly altered metabolites in A549-R cells compared to A549-P cells. Among the significantly upregulated proteins are liver carboxylesterase 1, anterior gradient protein 2 homolog and nicotinamide phosphoribosyltransferase. A group of the upregulated proteins are endogenous and xenobiotic-metabolizing enzymes, including UDP-glucuronosyltransferase 1-6, CES1, and epoxide hydrolase 1. While Importin, ATP-citrate synthase and CTP synthase are downregulated. The significantly altered metabolites include sepiapterin, glutathione, glycine, pyridine and niacinamide. The performed multi-omics integrated analysis revealed the involvement of purine and glutathione metabolism, ABC transporters, citric acid cycle in the development of resistance in A549 cells, besides the involvement of energy metabolism, pathways related to cancer progression, invasion and migration, and redox homeostasis. Collectively, this exploratory study effectively revealed the significantly dysregulated proteins and metabolites in doxorubicin resistant A549 cells and shed the light on potential biomarkers for chemotherapy resistant non-small cell lung cancer. In addition, multi-omics integrated analysis elucidates the involved pathways in resistance including pathways related to progression and invasion which would improve prognosis and open the door for new potential therapeutic targets.
Institute	University of Sharjah
Department	Research institute of medical and health science
Laboratory	Biomarker Discovery Group
Last Name	Facility
First Name	Core
Address	M32, SIMR, College of Pharmacy, Health Sciences, University of Sharjah, Sharjah, UAE, Sharjah, 000, United Arab Emirates
Email	tims-tof@sharjah.ac.ae
Phone	+971 6 5057656
Submit Date	2023-05-04
Raw Data Available	Yes
Raw Data File Type(s)	d
Analysis Type Detail	LC-MS
Release Date	2023-11-30
Release Version	1

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Treatment:

Treatment ID:	TR002817
Treatment Summary:	The human non-small cell lung cancer cell line (A549) was purchased from AmericanType Culture Collection (ATCC) (Manassas, USA). A doxorubicin-resistant A549 (A549-R) cell line was generated in our laboratory (Drug Design and Discovery Research Group, Pharmacology Laboratory, Sharjah Institute for Medical Research, University of Sharjah). To develop resistant cells from the parental A549 cells (A549-P), A549-P cells were treated with a tenth of Dox's maximal inhibitory concentration (IC10). The surviving population of cells was cultured in a new flask and treated with a gradual increase of Dox concentration for 8 months. Maintenance of A549-R cells resistance was at a dose of 0.02 µg/ml of Dox. A549-P and A549-R cells were cultured in a Dulbecco's Modified Eagle Medium/ Nutrient Mixture F-12 (1:1) medium (DMEM/F-12) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. The cells were incubated in a humidified atmosphere of 5% CO2 at 37 ˚C.

Treatment ID:

TR002817

Treatment Summary:

The human non-small cell lung cancer cell line (A549) was purchased from AmericanType Culture Collection (ATCC) (Manassas, USA). A doxorubicin-resistant A549 (A549-R) cell line was generated in our laboratory (Drug Design and Discovery Research Group, Pharmacology Laboratory, Sharjah Institute for Medical Research, University of Sharjah). To develop resistant cells from the parental A549 cells (A549-P), A549-P cells were treated with a tenth of Dox's maximal inhibitory concentration (IC10). The surviving population of cells was cultured in a new flask and treated with a gradual increase of Dox concentration for 8 months. Maintenance of A549-R cells resistance was at a dose of 0.02 µg/ml of Dox. A549-P and A549-R cells were cultured in a Dulbecco's Modified Eagle Medium/ Nutrient Mixture F-12 (1:1) medium (DMEM/F-12) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. The cells were incubated in a humidified atmosphere of 5% CO2 at 37 ˚C.