Related Experiment Video
Updated: Apr 15, 2026
Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Identification of proteins responsible for adriamycin resistance in breast cancer cells using proteomics analysis
Zhipeng Wang1, Shuang Liang2, Xin Lian3
11] Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Haping Road 150 of Nangang District, Harbin 150081, Heilongjiang Province, China [2] Department of Medical Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Abstract:
Chemoresistance is a poor prognostic factor in breast cancer and is a major obstacle to the successful treatment of patients receiving chemotherapy. However, the precise mechanism of resistance remains unclear. In this study, a pair of breast cancer cell lines, MCF-7 and its adriamycin-resistant counterpart MCF-7/ADR was used to examine resistance-dependent cellular responses and to identify potential therapeutic targets. We applied nanoflow liquid chromatography (nLC) and tandem mass tags (TmT) quantitative mass spectrometry to distinguish the differentially expressed proteins (DEPs) between the two cell lines. Bioinformatics analyses were used to identify functionally active proteins and networks. 80 DEPs were identified with either up- or down-regulation. Basing on the human protein-protein interactions (PPI), we have retrieved the associated functional interaction networks for the DEPs and analyzed the biological functions. Six different signaling pathways and most of the DEPs strongly linked to chemoresistance, invasion, metastasis development, proliferation, and apoptosis. The identified proteins in biological networks served to resistant drug and to select critical candidates for validation analyses by western blot. The glucose-6-phosphate dehydrogenase (G6PD), gamma-glutamyl cyclotransferase (GGCT), isocitrate dehydrogenase 1 (NADP+,soluble)(IDH1), isocitrate dehydrogenase 2 (NADP+,mitochondrial) (IDH2) and glutathione S-transferase pi 1(GSTP1), five of the critical components of GSH pathway, contribute to chemoresistance.
Insights
Chemoresistance in breast cancer is poorly understood. This study identified key proteins in the glutathione (GSH) pathway, like G6PD and GSTP1, that contribute to drug resistance and could be therapeutic targets.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Chemoresistance significantly worsens breast cancer prognosis and hinders effective chemotherapy.
- The exact molecular mechanisms driving chemoresistance remain largely unknown.
- Identifying novel therapeutic targets is crucial for overcoming treatment failure.
Purpose of the Study:
- To investigate chemoresistance-dependent cellular responses in breast cancer.
- To identify differentially expressed proteins (DEPs) associated with adriamycin resistance.
- To uncover potential therapeutic targets for overcoming chemoresistance.
Main Methods:
- Utilized nanoflow liquid chromatography (nLC) and tandem mass tags (TmT) quantitative mass spectrometry.
- Compared protein expression between MCF-7 and adriamycin-resistant MCF-7/ADR breast cancer cell lines.
- Employed bioinformatics and protein-protein interaction (PPI) network analyses.
Main Results:
- Identified 80 differentially expressed proteins (DEPs) between the cell lines.
- Discovered six signaling pathways and numerous DEPs linked to chemoresistance, invasion, metastasis, proliferation, and apoptosis.
- Validated five key glutathione (GSH) pathway components (G6PD, GGCT, IDH1, IDH2, GSTP1) as critical contributors to chemoresistance.
Conclusions:
- The glutathione (GSH) pathway plays a significant role in breast cancer chemoresistance.
- Proteins such as G6PD, GGCT, IDH1, IDH2, and GSTP1 are critical mediators of drug resistance.
- These identified proteins represent potential therapeutic targets for improving breast cancer treatment outcomes.
