[Effect of fluorouracil combined with FK228 on the proliferation, apoptosis and Fas mRNA level in HepG2 hepatoma cell lines].
OBJECTIVE
To explore the effect of fluorouracil (FU) combined with epigenetic drug FK228 (depsipeptide FR901228) on the proliferation, apoptosis and Fas mRNA level in HepG2 hepatoma cell lines.


METHODS
There were 4 groups in this experiment: an untreated group, an FK228 treated group, a FU treated group,and a FU combined with FK228 group.Tetrazolium salt colorimetry (MTT) assay was used to assess the cell inhibition rate. Q value of Kingos formula and multi-factor analysis of variance (ANOVA ) were used to judge the combination treatment effect,and flow cytometry was used to detect the apoptosis rate. Fas mRNA level was analyzed by RT-PCR.


RESULTS
FK228 or FU would inhibit the growth of HepG2 cells in a concentration-dependent and time-dependent manner. Cell inhibition rates of HepG2 were significantly enhanced in the FU combined with FK228 group, compared with that in the FU treated group alone (P<0.05). Both Q values were more than 1, the 2 drug combinations showed interaction,and FU combined with FK228 had synergistic effect.Compared with the FK228 treated group and the FU treated group, apoptosis rate of HepG2 cells was significantly increased (P<0.05), and the Fas mRNA level was up-regulated in HepG2 cells in FU combined FK228 group (P<0.05).


CONCLUSIONS
Combination of FK228 and FU can enhance the proliferation inhibition and apoptosis induction of FU in hepatoma cell lines, up-regulate the Fas mRNA level, and increase the sensitivity of hepatoma cell lines to FU.
Chen
Zhongnan
Z
Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China.
Xu
Keqian
K
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D047630:Depsipeptides / Q000494:pharmacology*; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D047630:Depsipeptides; C491901:FAS protein, human; D012333:RNA, Messenger; D019014:fas Receptor; C087123:romidepsin; D005472:Fluorouracil