Advancement of NK cell-mediated pancreatic cancer therapy through high-throughput screening

Pancreatic cancer remains a highly aggressive malignancy with limited effective treatment options, highlighting the need for alternative therapeutic strategies. This study aimed to identify compounds that modulate natural killer (NK) cell activity and to evaluate their effects on NK cell–associated responses against pancreatic cancer cells. Usinghigh-throughput screening (HTS), four candidate compounds were identified, among which rosiglitazone induced the most prominent increase in the expression of NK cell surface receptors, including NKp30 and NKp46, in NK-92MI cells. Cell viability and protein expression were assessed using a WST-8 assay and western blot analysis, respectively. Co-culture experiments were performed to evaluate NK cell–associated effects on pancreatic cancer cells. Rosiglitazone did not affect the viability of pancreatic cancer cells (Panc-1 and BxPC-3) and showed a tendency to increase NK-92MI cell viability. In co-culture conditions, rosiglitazone-treated NK-92MI cells were associated with reduced viability of pancreatic cancer cells, increased apoptosis, and altered expression of apoptosis-related proteins. These findings suggest that rosiglitazone modulates NK-92MI cell activity and may enhance NK cell–associated responses against pancreatic cancer cells in vitro. Further studies are required to validate these observations and to clarify the underlying mechanisms.