When drug repurposing backfires: antagonistic effects of ivermectin on cisplatin therapy in oral cancer.
4 affiliations
- 1Oral Medicine and Periodontology, Faculty of Dentistry, The British University in Egypt, El Sherouk City, Egypt. [email protected].
- 2Department of Pharmacology, Faculty of Dentistry, The British University in Egypt, El Sherouk City, Egypt.
- 3Dental Science Research Group, Health Research Centre of Excellence, The British University in Egypt (BUE), El Sherouk City, Egypt.
- 4Oral Medicine and Periodontology, Faculty of Dentistry, The British University in Egypt, El Sherouk City, Egypt.
Abstract
Background
Cisplatin (CIS) remains the gold standard chemotherapeutic agent for the management of oral cancer. However, its clinical efficacy is frequently limited by chemoresistance and dose-dependent toxicities. Ivermectin (IVM), a well-established antiparasitic agent with emerging anticancer properties, has been proposed as a potential adjuvant capable of enhancing the antitumor efficacy of CIS.Methods
In vitro experiments were conducted on HN9 oral squamous cell carcinoma cells, while OEC normal epithelial cells served as control. The experimental evaluation comprised the MTT assay for cell viability, Annexin V/propidium iodide (PI) staining for apoptosis detection, cell cycle distribution analysis, quantitative real-time PCR (RT-qPCR) for the assessment of apoptotic, anti-apoptotic, and inflammatory gene expression, and oxidative stress assay.Results
Contrary to expectations, the CIS-IVM combination demonstrated an antagonistic interaction in HN9 cells. This was evidenced by reduced cytotoxicity of the combination treatment compared to CIS monotherapy, as determined by the MTT assay. Additionally, the combination attenuated CIS-induced S-phase arrest and was associated with decreased expression of pro-apoptotic markers (BAX and Caspase-3). Differential modulation of TNF-α expression and glutathione levels further suggested complex interactions affecting inflammatory and oxidative stress pathways. These findings indicate that IVM may interfere with CIS-induced cytotoxicity, potentially through its antioxidant and anti-inflammatory properties.Conclusions
The present study demonstrated an unexpected antagonistic interaction between CIS and IVM in HN9 oral cancer cells. Further investigations are warranted to elucidate the underlying molecular mechanisms and to determine whether similar effects occur in other oral cancer models or in vivo settings.
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BibTeX
@article{tantawy2026when,
title = {{When drug repurposing backfires: antagonistic effects of ivermectin on cisplatin therapy in oral cancer.}},
author = {Rana Tantawy and Shereen Nader Raafat and Ayman El-Gawish and Dalia Ghalwash},
journal = {BMC pharmacology \& toxicology},
year = {2026},
month = oct,
doi = {10.1186/s40360-026-01198-w},
url = {https://europepmc.org/article/MED/42907850},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - When drug repurposing backfires: antagonistic effects of ivermectin on cisplatin therapy in oral cancer.
AU - Rana Tantawy
AU - Shereen Nader Raafat
AU - Ayman El-Gawish
AU - Dalia Ghalwash
PY - 2026
DA - 2026/10/20
JO - BMC pharmacology & toxicology
DO - 10.1186/s40360-026-01198-w
UR - https://europepmc.org/article/MED/42907850
AB - Background Cisplatin (CIS) remains the gold standard chemotherapeutic agent for the management of oral cancer. However, its clinical efficacy is frequently limited by chemoresistance and dose-dependent toxicities. Ivermectin (IVM), a well-established antiparasitic agent with emerging anticancer properties, has been proposed as a potential adjuvant capable of enhancing the antitumor efficacy of CIS.Methods In vitro experiments were conducted on HN9 oral squamous cell carcinoma cells, while OEC normal epithelial cells served as control. The experimental evaluation comprised the MTT assay for cell viability, Annexin V/propidium iodide (PI) staining for apoptosis detection, cell cycle distribution analysis, quantitative real-time PCR (RT-qPCR) for the assessment of apoptotic, anti-apoptotic, and inflammatory gene expression, and oxidative stress assay.Results Contrary to expectations, the CIS-IVM combination demonstrated an antagonistic interaction in HN9 cells. This was evidenced by reduced cytotoxicity of the combination treatment compared to CIS monotherapy, as determined by the MTT assay. Additionally, the combination attenuated CIS-induced S-phase arrest and was associated with decreased expression of pro-apoptotic markers (BAX and Caspase-3). Differential modulation of TNF-α expression and glutathione levels further suggested complex interactions affecting inflammatory and oxidative stress pathways. These findings indicate that IVM may interfere with CIS-induced cytotoxicity, potentially through its antioxidant and anti-inflammatory properties.Conclusions The present study demonstrated an unexpected antagonistic interaction between CIS and IVM in HN9 oral cancer cells. Further investigations are warranted to elucidate the underlying molecular mechanisms and to determine whether similar effects occur in other oral cancer models or in vivo settings.
SN - 2050-6511
ER -