We investigated the effects of 5-fluorouracil (FU) to the cervical cancer cell lines with HPV in the aspect of the apoptosis and HPV.

The effects of 5-FU on apoptosis was studied using a proteomic method based on a two dimensional gel electrophoresis and MALDI-TOF-MS using peptide mass fingerprinting.

More than 50 proteins showed a significant change in 5-FU treated cervical carcinoma cells compared to control cells. Among them, 34 proteins have been identified and 22 proteins were up-regulated CIDE-B (cell death inducing DFFA-like effector B), caspase-3, caspase-8 and Apo-1/CD95 (Fas), etc and 12 proteins were down-regulated mitotic checkpoint protein BUB3, myc proto-oncogene protein (c-myc), src substrate cortactin and transforming protein p21A, etc by 5-FU treatment in HeLa cells as determined by spot volume (P<0.05). Our experiments showed that 5-FU engaged the mitochondrial apoptotic pathway involving cytosolic cytochrome c release and subsequent activation of caspase-9 and caspase-3 as well as the membrane death receptor (DR)-mediated apoptotic pathway involving activation of caspase-8 with an Apo-1/CD95 (Fas)-dependent fashion. In addition, we could observe reduction of HPV-18 E6/E7 gene expression and activation of p53, pRb and p21(waf1) proteins by 5-FU treatment in HeLa cells.

we suggest that 5-FU suppresses the growth of cervical cancer cells not only by anti-proliferative effect but also anti-viral regulation. Our findings may offer new insights into the mechanism of anticancer effect affected by 5-FU treatment in cervical cancer cells and its mode of action.