Abstract: OBJECTIVE： To investigate the characteristics and mechanisms of cisplatin-induced polyploid giant cancer cells (PGCCs) in vitro. METHODS： Cultured cells were treated with cisplatin at concentrations of 1.5，3，6，12，and 24 μg/mL for 3，4，and 5 days. DNA content was analyzed by flow cytometry to determine the optimal combination of concentration and duration for PGCC induction in A549，HepG2，and SK-OV-3 cells. Morphological changes and DNA nuclear area were examined through morphological observation and Giemsa staining. Expression of stemness genes (Nanog，Sox-2，OCT-4，c-Myc) was evaluated by RT-qPCR，while stemness surface markers (CD44，CD133) were analyzed by flow cytometry. Cell senescence was assessed by β-galactosidase staining. After 72-hour treatment with cisplatin at concentrations ranging from 0.75 to 96 μg/mL，cell viability was measured by the MTT assay. RESULTS： Treatment with 3 μg/mL cisplatin for 3 d effectively induced polyploidy (>4N) in all three cell lines. The induced cells exhibited significantly increased cell and nuclear areas；varying degrees of upregulation in stemness markers CD44 and CD133，along with partial increase in stemness gene expression；partial senescence phenotype in A549 cells；and enhanced cisplatin tolerance in A549 and SK-OV-3 PGCCs compared to controls. CONCLUSION： The cisplatin-induced PGCC model in A549 cells demonstrated enlarged cell and nuclear areas，expressed stemness genes (Nanog，Sox-2，OCT-4)，and showed increased cisplatin tolerance. The model may be useful for investigating，drug resistance mechanisms.

Key words: cisplatin, polyploid giant cancer cell, A549 cells, HepG2 cells, SK-OV-3 cells