Arsenic Trioxide Inhibited The Growth Of Trasplanted Tumor Of Human Gallbladder Carcinoma And Its Mechanism In Nude Mice

Background:Gallbladder carcinoma,a common carcinoma in biliary system,lacking of specific clinical manifestation,usually diagnosed at advanced stages of the diseases and fewer can be resected in operation.Chemotherapy and radiotherapy has not shown significant activity in gallbladder carcinoma,so new agent should be applied to its treatment.Arsenic trioxide,verified as a breakthrough in the management of acute promyelocytic leukemia,has been applied to the research and the therapy of a variety of solid tumors in recent years.However,the research into the effect of As₂O₃ on gallbladder carcinoma has not been widely reported.Purpose:To investigate the inhibitory effect of As₂O₃ on the growth of transplanted tumor of human gallbladder carcinoma and its mechanism in nude mice.Methods:Twenty BALB/c nude mice,with the resembling volume of subcutaneous transplanted tumor,were randomly divided into nature saline(NS) and As₂O₃ groups. 0.2mL NS or 10mg As₂O₃/kg was injected into the tail vain of every mouse in NS group or As₂O₃ group for seven days,once per day.All mice were put to death fourteen days after the perfusion was performed,then the weight and dimension were assayed,the apoptosis cells were determined by TdT-mediated dUTP Nick-end Labeling(TUNEL) and counted as well as the expression of Bcl-2 and Cyclin D1 was detected by immunohistochemical method and Western Blot.Results:The volume and weight of transplanted tumor was 1.50±0.57cm³ and 0.992±0.401g in NS group,which reduced to 0.83±0.39cm³ and 0.526±0.269g in As₂O₃ group.The apoptosis cells were 22.2±3.79 in NS group,which elevated to 57.9±9.75 in As₂O₃ group.The expression of Bcl-2 and Cyclin D1 in As₂O₃ group was lower than that in NS group which was detected by immunohistochemical method and Western Blot.All the difference were significant.Conclusions:As₂O₃(10mg/kg) can significantly inhibit the growth of transplanted tumor of human gallbladder carcinoma in nude mice.The mechanism has correlation to inducing apoptosis and downregulating the expression of Bcl-2 and Cyclin D1.