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Effects of tacrolimus on proliferation, apoptosis, and fluorouracil sensitivity of liver cancer cell line of SMMC-7721 |
Xiao-Wei Cao, Zhi-Ren Fu and Guo-Shan Ding |
Shanghai, China
Author Affiliations: Organ Transplantation Institute of PLA, Liver Transplantation Group of Transplantation Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China( Cao XW, Fu ZR and Ding GS)
Corresponding Author: Zhi-Ren Fu, MD, Liver Transplantation Group of Transplantation Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China (Tel:86-21-63610109ext73306; Fax:86-21-63276788; Email: zhirenf@sh.163.net) |
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Abstract 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.
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