HIGH-RISK HPV-POSITIVE HUMAN CANCER CELL-LINES SHOW DIFFERENT SENSITIVITY TO CISPLATIN-INDUCED APOPTOSIS CORRELATED WITH THE P21(WAF1 CIP1)LEVEL/

We investigated the sensitivity and cell-cycle inhibitory gene express ion of human papillomavirus (HPV) 16- and 18-positive human cancer cel l lines after DNA damage induced by treatment with the anti-cancer dru g cisplatin. Four HPV-positive cell lines (Caski, SiHa, HeLa and KB) w ere treated with cisplatin at various concentrations. Apoptotic cell d eath was observed in a dose-dependent manner in all cell lines treated with cisplatin; however, colony assay for chemosensitivity revealed t hat HeLa and KB cells (HPV 18-positive cell lines) were more sensitive than SiHa and Caski cells (HPV 16-positive cell lines). Northern blot analyses showed that p53 and p21(Wafl/Cipl) mRNA were detectable in a ll untreated cells, and increasing amounts of these transcripts were i dentified in all cell lines treated with cisplatin. However, signals w ere more prominent in HeLa and KB, HPV 18-positive-cells. Immunohistoc hemical detection of p21(Wafl/Cipl) protein showed that the p21-positi ve cells with apoptotic features were more distinct in KB and HeLa cel ls (HPV 18-positive) than in SiHa and Caski cells (HPV 16-positive). O ur results show that there were differences in sensitivity to cisplati n among four types of high risk HPV-positive cells, possibly due to di fferent levels of p21(Wafl/Cipl) up-regulation by functional p53.