Evidence of cisplatin-induced senescent-like growth arrest in nasopharyngeal carcinoma cells

Abstract

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 β-galactosidase (SA-β-gal). This senescent-like change was dose related; at 0.5 μg/ml, the percentage of cisplatin-induced SA-β-gal-positive cells was high (40-96%), and the staining was intense. Higher doses (1.0 and 2.0 μg/ml) of cisplatin induced lower SA-β-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 senescent-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.