iTRAQ quantitative analysis of multidrug resistance mechanisms in human gastric cancer cells
Huai-Dong Hu1, Feng Ye, Da-Zhi Zhang
1Key Laboratory of Molecular Biology for Infectious Diseases of Ministry of Education of China, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Abstract:
Multidrug resistance (MDR) is a major obstacle towards a successful treatment of gastric cancer. However, the mechanisms of MDR are intricate and have not been fully understood. To elucidate the molecular mechanisms of MDR in gastric cancer, we employed the proteomic approach of isobaric tags for relative and absolute quantification (iTRAQ), followed by LC-MS/MS, using the vincristine-resistant SGC7901/VCR cell line and its parental SGC7901 cell line as a model. In total, 820 unique proteins were identified and 91 proteins showed to be differentially expressed in SGC7901/VCR compared with SGC7901. Several differentially expressed proteins were further validated by western blot analysis. Furthermore, the association of MVP, one of the highly expressed proteins in SGC7901/VCR, with MDR was verified. Our study is the first application of iTRAQ technology for MDR mechanisms analysis in gastric cancer, and many of the differentially expressed proteins identified have not been linked to MDR in gastric cancer before, which showed the value of this technology in identifying differentially expressed proteins in cancer.
Insights
This study investigated multidrug resistance (MDR) in gastric cancer using proteomic analysis. We identified 91 differentially expressed proteins, including MVP, offering new insights into gastric cancer drug resistance mechanisms.
Area of Science:
- Proteomics
- Molecular Biology
- Oncology
Background:
- Multidrug resistance (MDR) presents a significant challenge in gastric cancer treatment.
- The molecular mechanisms underlying gastric cancer MDR remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of MDR in gastric cancer.
- To identify novel protein biomarkers associated with MDR in gastric cancer.
Main Methods:
- Proteomic analysis using isobaric tags for relative and absolute quantification (iTRAQ) coupled with LC-MS/MS.
- Utilized vincristine-resistant (SGC7901/VCR) and parental (SGC7901) gastric cancer cell lines as a model.
- Western blot analysis for validation of differentially expressed proteins.
Main Results:
- Identified 820 unique proteins, with 91 proteins exhibiting differential expression between resistant and parental cell lines.
- Confirmed the association of Multiviscin-like Protein 1 (MVP) with MDR in gastric cancer.
- Several novel proteins linked to MDR were discovered.
Conclusions:
- This study represents the first application of iTRAQ technology to analyze MDR mechanisms in gastric cancer.
- The identified differentially expressed proteins, particularly MVP, provide valuable targets for understanding and potentially overcoming gastric cancer MDR.
- Highlights the utility of advanced proteomic techniques in cancer research.
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