Effect of fluorouracil combined with FK228 on the proliferation, apoptosis and Fas mRNA level in HepG2 hepatoma cell lines.
- Author:
Zhongnan CHEN
1
;
Keqian XU
Author Information
1. Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China.
- Publication Type:Journal Article
- MeSH:
Antibiotics, Antineoplastic;
pharmacology;
Antimetabolites, Antineoplastic;
pharmacology;
Apoptosis;
drug effects;
Cell Proliferation;
drug effects;
Depsipeptides;
pharmacology;
Drug Synergism;
Fluorouracil;
pharmacology;
Hep G2 Cells;
Humans;
RNA, Messenger;
genetics;
metabolism;
fas Receptor;
genetics;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2009;34(2):124-129
- CountryChina
- Language:Chinese
-
Abstract:
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).
CONCLUSION: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.
