Published online Sep 15, 2000. doi: 10.3748/wjg.v6.iSuppl3.23
Revised: June 24, 2000
Accepted: July 10, 2000
Published online: September 15, 2000
AIM: To study the effect of a wide range of concentration of arsenic trioxide on human hepatoma cell line BEL-7402 and its mechanism.
METHODS: The BEL-7402 cells were treated with arsenic trioxide (a final concentration of 0.5, 1 and 2 μmol/L, respectively) in various durations or for 4 successive days. The cell growth and prolife ration were observed by cell counting and cell-growth curve. Morphologic change s were studied under electron microscopy. Flow cytometry was used to assay cell DNA distribution and the protein expression of Bcl-2 and Bax was detected by immunocytochemical method.
RESULTS: The cell growth was significantly inhibited by the different concentrations of arsenic trioxide as revealed by cell counting and cell growth curve. Arsenic trioxide treatment at 0.5, 1 and 2 μmol/L, resulted in a sub-G1 cell peak. The decreased G0/G1 phase cell and the increased percentage of S phase cell were observed by flow cytometer, suggesting that the inhibiting effect of arsenic trioxide on BEL-7402 cell lay in G0/G1 phase cell. Apoptotis related morphology, such as intact cell membrane, nucleic condensation, apoptotic body formation, can be seen under the electron microscopy. High protein expression level of Bcl-2 and Bax was detected in 1 and 2 μmol/L arsenic trioxide treated cells, but that of Bax was more significant. Arsenic trioxide treatment at 0.5 μmol/L resulted in higher expression level of Bcl-2 and lower expression level of Bax compared with control (P1≤ 0.01, P2 < 0.01).
CONCLUSION: Arsenic trioxide not only inhibited the proliferation but also induced apoptosis of human hepatoma cell line BEL-7402. The induced apoptosis effect of 1 and 2 μmol/L arsenic trioxide was relative to the expression level of Bcl-2 and Bax.