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

Departments of Pathology [X. W., K. H. Y. F., J. M. N.], Anatomy [S. C. H. W., J. P., S. W. T.], and Radiation Oncology [D. L. W. K., J. S. T. S.], University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China

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-ß-gal). This senescent-like change was dose related; at 0.5 µg/ml, the percentage of cisplatin-induced SA-ß-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-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 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.

¹ This work was supported by the Hong Kong Research Grant Council (No. 338/046/0011), the University of Hong Kong (CRCG Grant No. 337/037/0001, 335/037/0002), the Li Ka Shing Foundation, the Hong Kong Jockey Club (Charity) Ltd., the Ho Hung Chiu Foundation, and Croucher Foundation, Hong Kong.

² To whom requests for reprints should be addressed, at Department of Pathology, University of Hong Kong, Queen Mary Hospital, Pok Fu Lam Road, Hong Kong, People's Republic of China. Phone: (852) 2855 4883; Fax: (852) 2872 5197; E-mail: jmnichol@hkucc.hku.hk.

Received 8/ 6/98. Accepted 9/28/98.

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