Effects of tacrolimus on proliferation, apoptosis, and fluorouracil sensitivity of liver cancer cell line of SMMC-7721.

BACKGROUND

The effect of tacrolimus (FK506) and 5-fluorouracil (5-FU) on hepatocellular carcinoma remains elusive. The aim of this study was to assess the effect of tacrolimus on the proliferation, and apoptosis in liver cancer cell line of SMMC-7721 and its sensitivity to fluorouracil (5-FU).

METHODS

The liver cancer cell line of SMMC-7721 was cultured in vitro, and the MTT assay was used to examine the antiproliferative effect of FK506. Flow cytometry (FCM) was used to examine the effect of 5-FU alone or in combination with FK506 on the apoptosis and cell cycle of SMMC-7721 cells.

RESULTS

FK506 produced concentration-dependent antiproliferative effect on SMMC-7721 cells at all experimental concentrations (P<0.05), but no effect on induction of apoptosis. 5-FU induced apoptosis in a concentration-dependent manner, whereas the percentage of G0/G1-phase cells and proliferation index (PI) were increased with the increased concentration of 5-FU. Pretreatment with FK506 for 2 hours enhanced the effect of 5-FU on the induction of apoptosis.

CONCLUSIONS

FK506 inhibits the growth of SMMC-7721 cells and enhances their sensitivity to 5-FU. This may be associated with the synergic effect of FK506 and 5-FU in inducing apoptosis and G0/G1-phase stasis.