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Updated: Dec 5, 2025
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Sequenced Combinations of Cisplatin and Selected Phytochemicals towards Overcoming Drug Resistance in Ovarian Tumour
Safiah Ibrahim Althurwi1, Jun Q Yu1, Philip Beale2
1School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia.
Abstract:
In the present study, cisplatin, artemisinin, and oleanolic acid were evaluated alone, and in combination, on human ovarian A2780, A2780ZD0473R, and A2780cisR cancer cell lines, with the aim of overcoming cisplatin resistance and side effects. Cytotoxicity was assessed by MTT reduction assay. Combination index (CI) values were used as a measure of combined drug effect. MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis were used to identify protein biomarkers in ovarian cancer and to evaluate combination effects. Synergism from combinations was dependent on concentration and sequence of administration. Generally, bolus was most synergistic. Moreover, 49 proteins differently expressed by 2 ≥ fold were: CYPA, EIF5A1, Op18, p18, LDHB, P4HB, HSP7C, GRP94, ERp57, mortalin, IMMT, CLIC1, NM23, PSA3,1433Z, and HSP90B were down-regulated, whereas hnRNPA1, hnRNPA2/B1, EF2, GOT1, EF1A1, VIME, BIP, ATP5H, APG2, VINC, KPYM, RAN, PSA7, TPI, PGK1, ACTG and VDAC1 were up-regulated, while TCPA, TCPH, TCPB, PRDX6, EF1G, ATPA, ENOA, PRDX1, MCM7, GBLP, PSAT, Hop, EFTU, PGAM1, SERA and CAH2 were not-expressed in A2780cisR cells. The proteins were found to play critical roles in cell cycle regulation, metabolism, and biosynthetic processes and drug resistance and detoxification. Results indicate that appropriately sequenced combinations of cisplatin with artemisinin (ART) and oleanolic acid (OA) may provide a means to reduce side effects and circumvent platinum resistance.
Insights
This study explored combining cisplatin with artemisinin and oleanolic acid to overcome ovarian cancer cisplatin resistance. Certain drug combinations and administration sequences showed synergistic effects, identifying key protein biomarkers for drug resistance.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Cisplatin resistance and side effects are significant challenges in ovarian cancer treatment.
- Novel therapeutic strategies are needed to improve patient outcomes.
Purpose of the Study:
- To evaluate the efficacy of combining cisplatin with artemisinin and oleanolic acid in overcoming cisplatin resistance in ovarian cancer.
- To identify protein biomarkers associated with drug resistance and combination effects.
Main Methods:
- Cytotoxicity was assessed using MTT reduction assay.
- Combination Index (CI) values measured drug interaction.
- MALDI TOF/TOF MS/MS and 2-DE gel electrophoresis identified differentially expressed proteins.
Main Results:
- Synergistic effects were observed with specific drug combinations and administration sequences (bolus administration was most synergistic).
- 49 proteins were found to be differentially expressed, playing roles in cell cycle, metabolism, and drug resistance.
- Identification of specific up-regulated and down-regulated proteins in cisplatin-resistant cells.
Conclusions:
- Combinations of cisplatin with artemisinin and oleanolic acid show potential for overcoming platinum resistance in ovarian cancer.
- Appropriate sequencing of drug administration is crucial for maximizing synergistic effects.
- Understanding protein biomarker expression can guide targeted therapy development.
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