Combination of arsenic trioxide and ascorbic acid inhibits proliferation and induces apoptosis in human hepatoma cell line
YAN Xiao-Yu, SHI Jian-Guo, YAN Qing-Guo, CHEN Sheng-Quan, ZHANG Zhi-Pei, LI Qin-Long, ZHANG JingDepartment of Pathology, School of Basic Medicine, Fourth Military Medical University, Xi'an 710033, China
AIM: To study the synergistic effect of ascorbic acid (AA) and arsenic trioxide (As 2O 3) on the inhibition of proliferation and the induction of apoptosis in hepatoma cell line and to explore the effect of cellular glutathione (GSH) level on As 2O 3. METHODS: HepG2 cells were treated with As 2O 3 alone or in combination with AA. The viability of cells was determined by Trypan-blue assay and sub-G1 cells were detected by flow cytometry (FCM). The apoptosis rate was assessed by AnnexinV-PI staining and the GSH content was detected by GSH assay. RESULTS: 100 μmol/L AA had no influence on the proliferation and apoptosis in HepG2 cells. With As 2O 3 at the dosage of 2 μmol/L and 5 μmol/L, the combination of As 2O 3 and AA effectively enhanced the growth inhibition, compared to separate use of either alone. The cells treated by the two agents potentiated the apoptosis rate, compared with that of As 2O 3 alone. When cells were treated with AA or As 2O 3, the intracellular GSH content decreased markedly. The intracellular GSH content decreased significantly in cells treated with two agents, compared with that of As 2O 3 alone. CONCLUSION: The intracellular GSH content plays an important role in As 2O 3. Combined use of AA and As 2O 3 can made HepG2 cells more sensitive to As 2O 3 by decreasing the GSH level.
【CateGory Index】： R735.7