Induction of cell cycle arrest and apoptosis by 5-fluorouracil in laryngeal cancer cells containing HPV16 E6 and E7 oncoproteins.
OBJECTIVE
To investigate the cytotoxic effect of 5-fluorouracil (5Fu) on HPV16-associated laryngeal cancer cells.


METHODS
Cytotoxicity assay and TUNEL assay were used to assess the effect of 5Fu on laryngeal cancer cells transfected with HPV16 E6 or E7.


RESULTS
5Fu induced apoptosis in the cells either with or without HPV16 in a dose- and time-dependent manner. 5Fu caused the accumulation of active pRb and p21(WAF1/CIP1), together with an increase in Bak and Bax expression and a decrease in Bcl-2 levels in all the transfected cells. G(1)/S phase cell cycle arrest was associated with the antiproliferation activity of 5Fu. 5Fu also presented some effects on the E6 and E7 oncoproteins.


CONCLUSIONS
HPV16 E6 and E7 oncoproteins do not prevent 5Fu-medicated apoptosis and G(1)/S cell arrest in laryngeal cancers. The sensitivity of 5Fu treatment is associated with the decrease of Bcl-2 and/or the increase in Bak and p21(WAFI/CIP1).
Liu
Han Ching
HC
Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Chen
George G
GG
Vlantis
Alexander C
AC
Tong
Michael C F
MC
Chan
Paul K S
PK
van Hasselt
C Andrew
CA
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015513:Oncogene Proteins / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D014162:Transfection; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism
C475820:CCNE1 protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; C068651:E6 protein, Human papillomavirus type 16; D015513:Oncogene Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D050998:bcl-2 Homologous Antagonist-Killer Protein; C059731:oncogene protein E7, Human papillomavirus type 16; D005472:Fluorouracil