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. Design and 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 p21WAF1/CIP1, together with an increase in Bak and Bax expression and a decrease in Bcl-2 levels in all the transfected cells. G1/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 G1/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 p21WAFI/CIP1.