塞来昔布阻断 COX-2/PGE(2) 轴通过激活 NK 细胞增强抗 PD-1 对射频消融后残留肝细胞癌的疗效

In vitro, ELISA was used to assess the effects of radiofrequency heat treatment and celecoxib on PGE2 secretion by Hepa1-6 cells. Scanning electron microscopy, flow cytometry, and CCK-8 assays were employed to evaluate the function and cytotoxic activity of NK92 cells against Hepa1-6 cells. In vivo, orthotopic HCC mice were divided into five groups to evaluate tumor volume, pathology, and survival. The role of celecoxib in the COX-2/PGE2/NK cell axis and its impact on NK cell immune function were investigated.

In vitro experiments showed that celecoxib reversed PGE2-mediated suppression of NK cell function and cytotoxic activity against HCC cells by inhibiting PGE2 secretion. In vivo, orthotopic HCC mice treated with celecoxib and PD-1 exhibited significantly reduced tumor volumes, attenuated the infiltration and activation of NK cells, and prolonged survival compared to control groups. The combination therapy also demonstrated a notable abscopal-like effect, inhibiting metastatic tumor growth and activating systemic immunity.

Taken together, these findings suggest that celecoxib combined with PD-1 represents a promising strategy for treating residual HCC after RFA, with enhanced anti-tumor effects and good safety.