Experimental Study Of Apoptosis-inducing Effects Of Arsenic Trioxide On Human Cholangiocarcinoma Cell Line QBC939

Background Cholangiocarcinoma is the number two malignant tumor in hepatobiliary system, which of incidence is increasing in recent year, but, the effects of current treatment including surgery, conventional chemotherapy and radiation are still poor. So new efffective therapeutic approaches are very important. Since arsenic trioxide (AS2O3) had been applied for the treatment of acute promyelocytic leukemia (APL) successfully, in vitro studies on the molecular mechanism of AS2O3 on APL cells showed that the inhibition on cell proliferation was duo to direct induction of apoptosis through down-regulation of bcl-2 expression and modulation of PML-RAR a /PML protein. Furthermore, the apoptosis effect of AS2O3 can be observed in various cell lines of either myeloid or solid origin. However, there are still not much more reports in domestic and outside that arsenic trioxide was applied on the study of human cholangiocarcinoma cell line. In this study, we would provide a few certain proofs for clinic therapy with As2O3 through evaluting the growth-inhibiting and apoptosis-inducing effects of arsenic trioxide on human cholangiocarcinoma cell line QBC939 cultured in vitro.Objective To investigate the effects of arsenic trioxide on human cholangiocarcinoma cell line QBC939 and its mechanism. Methods Human cholangiocarcinoma cell line QBC939 was dividedinto control and experiment groups to culture. The experiment groups cellwas treated with different concentration of arsenic trioxide and control groups without it. At the state of culturing, observe the morphology of cell of experiment groups and control in culture flask by invert microscope every day. Growth inhibition/apoptosis and cell cycle changes of QBC939 cell line induced by arsenic trioxide were measured by means of MTT/flow cytometry/electronic microscope/DNA ladder determinations. RT-PCR technique was used to investigate the transcriptional changes of gene p53/bcl-2/bax.Results (1) The growth inhibition of QBC939 cell line induced by arsenic trioxide was enhanced in time-dependent and dose-dependent pattern and the highest inhibitory rate was 4.0 u mol/L. (2) Apoptosis was detected by eletronic microscope/flow cytometry/DNA ladder determinations. At same time S~G2/M retardation was founded. (3) RT-PCR showed that arsenic trioxide induced up regulation of bax and down regulation of bcl-2.Conclusions In vitro arsenic trioxide can inhibit the growth of QBC939 cell line and induce apoptosis. Its mechanism may correlate with the up-regulation of bax and down regulation of bcl-2.