Background and Objective: Rosiglitazone is a peroxisome proliferators-activated receptor γ (PPARγ) ligand, which inhibits tumor growth by activating PPARγ signaling pathways. Fluorouracil (5-FU) is one of the commonly used chemotherapeutic drugs. However, patients develop drug resistance of 5-FU over time. The aim of this study was to investigate whether rosiglitazone can enhance 5-FU-induced cell growth inhibition and to explore its potential mechanisms.Methods: Cell viability was measured using MTT assay. Protein expression levels were detected by Western blot analysis. Small interference RNA was utilized to knockout PPARγ and PTEN in Hep3B cells. Results: After 48 h of treatment with 10, 20, and 40 μmol/L rosiglitazone, the viability of Hep3B cells was (78.0 ± 2.7)%, (37.3 ± 8.1)%, and (19.8 ± 2.2)%, respectively (compared with control group, P values were all < 0.001). After 48 h of treatment with 10 μmol/L 5-FU, the viability of Hep3B cells was about (82.6 ± 3.9)%. When cells were treated with 10 μmol/L 5-FU in combination with either 10, 20 or 40 μmol/L rosiglitazone, the cell viability was (51.6 ± 5.4)%, (14.8 ± 4.2)%, and (8.5 ± 0.9)%, with corresponding q value of 1.36, 1.23, and 1.19, respectively. These data suggested that the two drugs had synergic effect in inhibiting Hep3B cell growth, which was further confirmed in an in vivo mice model. Subsequent investigations showed that rosiglitazone activated PPARγ signaling pathways and increased the expression of PTEN. Conclusions: Rosiglitazone enhances 5-FU-induced cell growth inhibition of Hep3B cells.
Liang-Qi Cao Zi-Li Shao He-Ping Peng Jian-Bin Xiao Ting Xia
