Experimental research of arsenic trioxide on human pancreatic carcinoma cell

OBJECTIVE To explore the inhibition effect of arsenic trioxide(As2O3) on human pancreatic carcinoma cell line PC-3 and its mechanism.METHODS CCK-8 assay was used to observe the inhibitory actions of As2O3 on PC-3 cells at various concentrations and for various times.The apoptotic rate and growth cycle of the cells were detected by flow cytometry and fluorescence microscope.The changes of the cells ultrastructures were observed under electron microscope.The expression of apoptosis-related gene protein(Bcl-2 and Bax) was detected by immunohistochemical staining.RESULTS As2O3 inhibited the proliferation of PC-3 cells in a concentration-and time-dependent manner.Lots of early apoptotic cell(FITC+/PI—) were detected by fluorescence microscope.Marked apoptosis peak was observed and the cells were mainly blocked in G1 phase(55.19%-85.80%).PC-3 cells showed obvious feature of apoptosis under electron microscope,such as intact cell membrane,concentration of plasma,pyknosis of chromatin and nuclear fragmentation.Bcl-2 protein were strongly expressed (+++) in controls,but weakly expressed(+) in As2O3-treated cells.Bax protein were weakly(+) expressed in controls respectively,but strongly expressed(+++) in As2O3-treated cells.CONCLUSION As2O3 can not only inhibit the proliferation but also induce the apoptosis of human pancreatic carcinoma cell PC-3.The mechanism is probably related to its effect on the regulation of Bcl-2 and Bax expression.