Related Experiment Video
Updated: Jul 18, 2026
Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
[Proteomic analysis of human ovarian cancer cell lines and their platinum-resistant clones]
1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Objective:
To perform comparative proteomic analysis of human ovarian cancer cell lines for detecting platinum-resistance associated proteins.
Methods:
The total proteins of two sensitive (SKOV3 and A2780) and four resistant (SKOV3/CDDP, SKOV3/CBP, A2780/CDDP and A2780/CBP) human ovarian cancer cell lines were separated by two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were analyzed using image analysis software, stained with Coomassie Brilliant Blue, then identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and database searching. The mRNA and protein levels of the differentially expressed protein which was most significant in all of the four resistant cell lines were validated by RT-PCR and western blotting, respectively.
Results:
Five proteins were found to be significant in four cell lines. Annexin A3 and destrin were up-regulated and nicotinamide-adenine dinucleotide phosphate (NADP)-dependent isocitrate dehydrogenase 1 was down-regulated in all the four resistant samples. Glutathione transferase omega 1 had an increased expression in the other three resistant cell lines except for SKOV3/CBP in which its expression was not changed. However, cofilin 1 represented a different trend. In the two resistant sublines of SKOV3, cofilin 1 had a down-regulation, but it had an up-regulation in the cell lines induced from SKOV3. The expression of annexin A3 was up-regulated by 3 - 20 fold and the results of RT-PCR and western blotting showed complete consistency with that by 2-DE.
Conclusions:
Proteomic techniques are useful to the identification of the resistance-associated proteins in ovarian cancer platinum-resistant cell lines and five candidates have been found. The five differential proteins might become hopeful candidate biomarkers for resistance.
Insights
Proteomic analysis identified five key proteins associated with platinum resistance in ovarian cancer cell lines. These proteins, including annexin A3 and destrin, may serve as novel biomarkers for predicting and overcoming drug resistance.
Area of Science:
- Proteomics
- Biochemistry
- Molecular Biology
Context:
- Ovarian cancer is a leading cause of cancer-related deaths in women.
- Platinum-based chemotherapy is a cornerstone treatment for ovarian cancer.
- Acquired platinum resistance remains a major challenge in ovarian cancer treatment.
Purpose:
- To identify proteins associated with platinum resistance in human ovarian cancer cell lines using comparative proteomic analysis.
- To detect differentially expressed proteins in sensitive and resistant ovarian cancer cell lines.
Summary:
- Comparative proteomic analysis using 2D-gel electrophoresis and MALDI-TOF-MS identified five significant proteins in platinum-resistant ovarian cancer cell lines.
- Annexin A3 and destrin were upregulated, while NADP-dependent isocitrate dehydrogenase 1 was downregulated in resistant cells.
- Glutathione transferase omega 1 and cofilin 1 showed varied expression patterns across different resistant cell lines.
Impact:
- The identified proteins, particularly annexin A3, may serve as potential biomarkers for platinum resistance in ovarian cancer.
- This study provides a foundation for developing strategies to overcome platinum resistance.
- Proteomic techniques are validated as effective tools for identifying resistance-associated proteins.
