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Peer-reviewedCC BY-NCJournal of Preventive and Complementary Medicine

Listeriolysin O, alone and in combination with Cisplatin and Carfilzomib, modulates MDR1, MRP1, and BCRP expression in Cisplatin-sensitive and -resistant ovarian cancer cells

  • Navid Ghasemzadeh1
  • Javad Zavar Reza2
  • Amir Hossein Fatehi Marj3
  • Moein Moradi4
  • Hooriya Takhtechian4
  • Sadegh Zarei5
5 affiliations
  1. 1Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  2. 2Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran
  3. 3Department of Laboratory Sciences, Faculty of Paramedicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  4. 4Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  5. 5Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
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Abstract

Background: Overexpression of ABC efflux transporters (MDR1, MRP1, BCRP) drives chemoresistance in ovarian cancer. We test a novel strategy combining the pore-forming toxin LLO with cisplatin and carfilzomib to overcome multidrug resistance.Objectives: This study aimed to evaluate the effects of LLO, both alone and in combination with Cis and CFZ, on the mRNA expression levels of MDR1, MRP1, and BCRP in cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CisR) human ovarian carcinoma cell lines.Methods: In this experimental study, A2780S and A2780CisR cells were treated for 72 hours with LLO, Cis, CFZ, and their combinations (Cis/LLO, CFZ/LLO, Cis/CFZ/LLO). The relative mRNA expression levels of MDR1, MRP1, and BCRP were quantified using quantitative real-time PCR (qRT-PCR), with normalization to the GAPDH housekeeping gene. Statistical analysis was performed using one-way ANOVA followed by Tukey's post-hoc test.Results: LLO monotherapy had a minimal impact on transporter expression. In stark contrast, all combination regimens induced a profound and statistically significant downregulation of MDR1, MRP1, and BCRP mRNA in both cell lines (p < 0.05 for overall treatment effect). The triple-combination therapy (Cis/CFZ/LLO) was the most potent, demonstrating the strongest suppression. The dual combination of CFZ/LLO was also highly effective. Notably, combinations involving CFZ were consistently potent in both sensitive and resistant cells, while the Cis/LLO combination showed differential efficacy, being less effective in A2780CisR cells.Conclusion: LLO acts as a powerful chemosensitizing agent that, in combination with cisplatin and carfilzomib, drastically downregulate the expression of critical ABC efflux transporters. This multi-mechanistic strategy, which concurrently targets DNA integrity, proteasome function, and plasma membrane stability, effectively overcomes a cornerstone of chemoresistance in ovarian cancer cells and represents a highly promising therapeutic approach for cisplatin-resistant disease.

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Cite

BibTeXRIS
BibTeX
@article{ghasemzadeh2026listeriolysin,
  title = {{Listeriolysin O, alone and in combination with Cisplatin and Carfilzomib, modulates MDR1, MRP1, and BCRP expression in Cisplatin-sensitive and -resistant ovarian cancer cells}},
  author = {Navid Ghasemzadeh and Javad Zavar Reza and Amir Hossein Fatehi Marj and Moein Moradi and Hooriya Takhtechian and Sadegh Zarei},
  journal = {Journal of Preventive and Complementary Medicine},
  year = {2026},
  month = oct,
  doi = {10.22034/jpcm.2026.590054.1384},
  url = {https://doi.org/10.22034/jpcm.2026.590054.1384},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Listeriolysin O, alone and in combination with Cisplatin and Carfilzomib, modulates MDR1, MRP1, and BCRP expression in Cisplatin-sensitive and -resistant ovarian cancer cells
AU  - Navid Ghasemzadeh
AU  - Javad Zavar Reza
AU  - Amir Hossein Fatehi Marj
AU  - Moein Moradi
AU  - Hooriya Takhtechian
AU  - Sadegh Zarei
PY  - 2026
DA  - 2026/10/25
JO  - Journal of Preventive and Complementary Medicine
DO  - 10.22034/jpcm.2026.590054.1384
UR  - https://doi.org/10.22034/jpcm.2026.590054.1384
AB  - Background: Overexpression of ABC efflux transporters (MDR1, MRP1, BCRP) drives chemoresistance in ovarian cancer. We test a novel strategy combining the pore-forming toxin LLO with cisplatin and carfilzomib to overcome multidrug resistance.Objectives: This study aimed to evaluate the effects of LLO, both alone and in combination with Cis and CFZ, on the mRNA expression levels of MDR1, MRP1, and BCRP in cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CisR) human ovarian carcinoma cell lines.Methods: In this experimental study, A2780S and A2780CisR cells were treated for 72 hours with LLO, Cis, CFZ, and their combinations (Cis/LLO, CFZ/LLO, Cis/CFZ/LLO). The relative mRNA expression levels of MDR1, MRP1, and BCRP were quantified using quantitative real-time PCR (qRT-PCR), with normalization to the GAPDH housekeeping gene. Statistical analysis was performed using one-way ANOVA followed by Tukey's post-hoc test.Results: LLO monotherapy had a minimal impact on transporter expression. In stark contrast, all combination regimens induced a profound and statistically significant downregulation of MDR1, MRP1, and BCRP mRNA in both cell lines (p < 0.05 for overall treatment effect). The triple-combination therapy (Cis/CFZ/LLO) was the most potent, demonstrating the strongest suppression. The dual combination of CFZ/LLO was also highly effective. Notably, combinations involving CFZ were consistently potent in both sensitive and resistant cells, while the Cis/LLO combination showed differential efficacy, being less effective in A2780CisR cells.Conclusion: LLO acts as a powerful chemosensitizing agent that, in combination with cisplatin and carfilzomib, drastically downregulate the expression of critical ABC efflux transporters. This multi-mechanistic strategy, which concurrently targets DNA integrity, proteasome function, and plasma membrane stability, effectively overcomes a cornerstone of chemoresistance in ovarian cancer cells and represents a highly promising therapeutic approach for cisplatin-resistant disease.
SN  - 3041-9700
SN  - 3041-9921
ER  -