The study, published in BMC Pharmacology and Toxicology, used several complementary measurements to characterize how the combination affected the cancer cells. In addition to the MTT viability assay, the researchers used Annexin V and propidium iodide staining to detect apoptosis, examined cell-cycle distribution and employed quantitative real-time PCR to assess expression of genes associated with apoptosis, resistance to apoptosis and inflammation. An oxidative-stress assay measured glutathione levels. OEC normal epithelial cells served as controls for the in vitro experiments.

Among the clearest findings was that ivermectin attenuated cisplatin-induced S-phase arrest in HN9 cells. Cisplatin alone increased the proportion of cells associated with S-phase arrest, while the combination reduced that response compared with cisplatin monotherapy. The combination was also associated with lower expression of the pro-apoptotic markers BAX and caspase-3 than cisplatin alone. These measured changes were consistent with the lower cytotoxicity observed in the viability assay. Together, the results show that ivermectin interfered with several cellular responses associated with cisplatin in this experimental model, rather than strengthening them.

The treatments also produced differential changes in two measures connected with inflammation and oxidative stress. Expression of tumor necrosis factor alpha, or TNF-α, and cellular glutathione levels varied across the single-drug and combination conditions. The researchers suggested that ivermectin’s antioxidant and anti-inflammatory properties may contribute to its antagonistic interaction with cisplatin. That proposed explanation was not isolated by the experiments, and the results do not establish which molecular process produced the antagonism. The study instead links the reduced cytotoxicity with attenuated S-phase arrest and diminished expression of pro-apoptotic markers while leaving the full mechanism unresolved.

These findings are limited to an in vitro study of one oral cancer cell line, with normal epithelial cells included as controls. The research does not demonstrate a clinical treatment effect, and it does not show how ivermectin and cisplatin would interact in patients. The authors stated that further investigations are needed to clarify the underlying molecular mechanisms and determine whether similar effects occur in other oral cancer models or in vivo settings. Within the tested HN9 cells, however, the evidence demonstrates that ivermectin reduced rather than amplified the cytotoxic, pro-apoptotic and cell-cycle-arresting effects associated with cisplatin.

Subject of Research: Antagonistic interaction between ivermectin and cisplatin in HN9 oral squamous cell carcinoma cells.

Article Title: When drug repurposing backfires: antagonistic effects of ivermectin on cisplatin therapy in oral cancer

Article References: Tantawy, R., Raafat, S. N., El-Gawish, A., & Ghalwash, D. (2026). When drug repurposing backfires: antagonistic effects of ivermectin on cisplatin therapy in oral cancer. BMC Pharmacology and Toxicology. https://doi.org/10.1186/s40360-026-01198-w

Image Credits: AI Generated

DOI: 10.1186/s40360-026-01198-w

Keywords: ivermectin, cisplatin, oral cancer, drug repurposing, drug antagonism, cell viability, apoptosis, cell-cycle arrest, oxidative stress, cancer cell lines, drug, repurposing