Evidence of Cisplatin-induced Senescent-like Growth Arrest in Nasopharyngeal Carcinoma Cells1

Cellular senescence is a programmed cell response leading to growth arrest in human diploid fibroblasts. We have shown that a nasopharyngeal carcinoma cell line, CNE1, following treatment by the DNA-damaging agent cisplatin, can undergo cellular senescent-like growth arrest, similar to fibroblasts, judged by cellular morphological changes and the expression of senescence-associated ß-galactosidase (SA-/3-gal). This se nescent-like change was dose related; at 0.5 fig/ml, the percentage of cisplatin-induced SA-/3-gal-positive cells was high (40-96%), and the staining was intense. Higher doses (1.0 and 2.0 jug/ml) of cisplatin induced lower SA-ß-gal expression (30-70%), and the process was irreversible. This cisplatin-induced cellular senescent-like response was not due to the inhibition of telomerase activity. Our results indicate that cellular senes cent-like pathways exist in nasopharyngeal carcinoma cells and can be induced by cisplatin. Our evidence suggests that cellular senescent-like responses may be a cellular protection mechanism that acts differently in response to different degrees of cellular damage.