High-risk HPV-positive human cancer cell lines show different sensitivity to cisplatin-induced apoptosis correlated with the p21Waf1/Cip1 level.
We investigated the sensitivity and cell-cycle inhibitory gene expression of human papillomavirus (HPV) 16- and 18-positive human cancer cell lines after DNA damage induced by treatment with the anti-cancer drug cisplatin. Four HPV-positive cell lines (Caski, SiHa, HeLa and KB) were treated with cisplatin at various concentrations. Apoptotic cell death was observed in a dose-dependent manner in all cell lines treated with cisplatin; however, colony assay for chemosensitivity revealed that 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 p21Waf1/Cip1 mRNA were detectable in all untreated cells, and increasing amounts of these transcripts were identified in all cell lines treated with cisplatin. However, signals were more prominent in HeLa and KB, HPV 18-positive-cells. Immunohistochemical detection of p21Waf1/Cip1 protein showed that the p21-positive cells with apoptotic features were more distinct in KB and HeLa cells (HPV 18-positive) than in SiHa and Caski cells (HPV 16-positive). Our results show that there were differences in sensitivity to cisplatin among four types of high risk HPV-positive cells, possibly due to different levels of p21Waf1/Cip1 up-regulation by functional p53.
Funaoka
K
K
Second Department of Oral Surgery, Hokkaido University School of Dentistry, Sapporo, Japan. funa@den.hokudai.ac.jp
Shindoh
M
M
Yamashita
T
T
Fujinaga
K
K
Amemiya
A
A
Totsuka
Y
Y
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016158:Genes, p53; D006367:HeLa Cells / Q000187:drug effects / Q000821:virology; D006801:Humans; D017403:In Situ Hybridization; D007624:KB Cells / Q000187:drug effects / Q000821:virology; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology / Q000821:virology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009369:Neoplasms / Q000473:pathology* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012306:Risk; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis; D014412:Tumor Virus Infections / Q000473:pathology* / Q000821:virology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin