Liposome-mediated Induction of Apoptosis of Human Hepatoma Cells by C-Myc Antisense Phosphorothioate Oligodeoxynucleotide and 5-Fluorouracil


Background: The aim of this study was to investigate the effect of a c-myc antisense oligodeoxynucleotideand 5-fluorouracil on the expression of c-myc, invasion and proliferation of HEPG-2 liver cancer cells. Materialsand
Methods: HEPG-2 cells were treated with lipiosome-mediated c-myc ADSON and 5-fluorouracil. Theproliferation inhibition rate and invasion were measured by MTT and invasion assay, respectively. Cell apoptosiswas detected by flow cytometry and expression of c-myc by RT-PCR and immunohistochemistry.
Results: Theproliferation inhibition rate was significantly higher in the antisense oligodeoxynucleotide added-5-fluorouracilgroup than single antisense oligodeoxynucleotide or 5-fluorouracil group (p<0.05). G0/G1 cells in the antisenseoligodeoxynucleotide group and S cells in the 5-fluorouracil groups were significantly increased than that in thecontrol group, respectively (P<0.01). The amplification strips of PCR products in 5-FU, ASODN and combinationgroups were significantly weaker than that in the control group (P<0.01). The percentage of c-myc-proteinpositivecells were significantly lower in antisense oligodeoxynucleotide, 5-fluorouracil and combination groupsthan that in the control group (P<0.01).
Conclusions: A liposome-mediated c-myc antisense oligodeoxynucleotideand 5-fluorouracil can inhibit the proliferation and invasion of liver cancer cells by reducing the expression ofc-myc. A c-myc antisense oligodeoxynucleotide can increase the sensitivity of liver cancer cells to 5-fluorouraciland decrease the dosage of the agent necessary for efficacy, providing an experimental basis for the clinicaltherapy of liver cancer.