Abstract: Abstract
Objective: To explore the mechanism by which I-125 radioactive particles induce pyroptosis in human liver cancer cells (HuH7). Methods: The subcellular structure changes of HuH7 cells after being irradiated by 8Gy I-125 radioactive particles were observed using transmission electron microscopy. The changes of the cell nuclei of HuH7 cells were observed using laser confocal microscopy. The correlation between the mortality rate of HuH7 cells induced by I-125 radioactive particles and the radiation dose was detected using flow cytometry. A HuH7 cell line tumor-bearing mouse model was constructed. I-125 radioactive particles were implanted into the transplanted tumors of nude mice to observe the morphological changes of the tumor tissues, determine the death mode of tumor cells induced by I-125 radioactive particles, and verify the regulatory pathways using WB experiments. Results: The transmission electron microscope showed that the I-125 radioactive particles could induce swelling in HuH7 cells, with local membrane rupture pores appearing and the number of pyroptotic bodies increasing. Under the laser confocal microscope, it was observed that HuH7 cells were swollen, enlarged, and showed multinucleated, fragmented, and abnormal nuclear changes. After 0Gy, 4Gy, 6Gy, and 8Gy radiation, the mortality rates of HuH7 cells were 0.49%, 0.87%, 2.20%, and 9.72% respectively, and the cell mortality rate was positively correlated with the radiation dose. A HuH7 cell tumor-bearing mouse model was constructed, and I-125 radioactive particles were implanted into the tumor of the model mice. Compared with the control group mice, the tumor tissues of the experimental group mice showed multinucleated and abnormal nuclear changes, and the surrounding tissue inflammation was obvious, presenting the morphological phenotype of pyroptosis. Through the WB experiment, it was verified that the I-125 radioactive particle radiation participated in the regulation of pyroptosis through the caspase-3/GSDME axis. Conclusion: The I-125 radioactive particles can induce a cell death pattern characterized by pyroptosis in the liver cancer HuH7 cells. This process is regulated by the caspase-3/GSDME axis.