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.
Cao
Xiao-Wei
XW
Liver Transplantation Group of Transplantation Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China. zhirenf@sh.163.net
Fu
Zhi-Ren
ZR
Ding
Guo-Shan
GS
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D008297:Male; D011336:Probability; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D016559:Tacrolimus / Q000494:pharmacology*
D005472:Fluorouracil; D016559:Tacrolimus