脐带血 NK 细胞来源外泌体通过靶向 ROS 介导的线粒体功能障碍抑制胰腺癌进展

Emerging research indicates that natural killer (NK) cell-derived exosomes (NK-exo) play a significant role in cancer development.

However, their regulatory mechanisms, particularly in pancreatic cancer, remain poorly elucidated.

This study employed an in vitro co-culture system and an in vivo subcutaneous tumor model to evaluate the anti-tumor effect of NK-exo on pancreatic cancer. Umbilical cord blood (UCB)-derived NK-exo displayed characteristic exosomal morphology, size, and marker expression and was internalized by PANC- 1 cells. NK-exo significantly and dose-dependently reduce cell proliferation, migration, and invasion (P < 0. 01).

Further analysis demonstrated that NK-exo induced mitochondrial apoptosis in PANC- 1 cells by altering reactive oxygen species (ROS, P < 0. 0001) and mitochondrial membrane potential (MPP) levels (P < 0. 0001), effects that were significantly diminished with N-acetylcysteine (NAC) treatment (P < 0. 0001).

Furthermore, NK-exo treated PANC- 1 cells showed upregulation of the apoptotic markers Caspase3 (P < 0. 0001) and Caspase9 (P = 0. 0086) and reduced the release of PGC- 1 (P = 0. 0064), TFAM (P < 0. 0001), and SOD2 (P = 0. 0021) as demonstrated by qRT-PCR.

Western blot analyses revealed a dose dependent significant elevation of total Caspase3, Caspase9, Bax, and cytochrome c level and depression in the anti-apoptotic Bcl- 2. Animal experiments further confirmed that NK-exo treatment significantly reduced tumor volume and weight and increased Bax protein expression relative to the tumor model group.

These findings indicate that NK-exo can enter PANC- 1 cells via endocytosis, induce mitochondrial oxidative damage, and suppress PANC- 1 cell progression, thereby demonstrating a robust anti-pancreatic cancer effect.