Effect Of Arsenic Trioxide On Human Uterine Sarcoma Cell Line MES-SA Transplanted Subcutaneously In Nude Mice

Objective: To study if arsenic trioxide（As₂O₃）has anti-tumor effect on human uterine sarcoma transplanted subcutaneously in nude mice in vivo,and preliminary study of its mechanism.Methods: Human uterine sarcoma cell line MES-SA was used for cell culture.Subcutaneous inoculation of cells into nude mice to created the tumor model.Use 40 nude mice（4-6 weeks old）for the experimental animals,divided into 5 groups:low-（1.0 mg/kg）,medium-（2.5 mg/kg）,and high-dose arsenic trioxide（5.0 mg/kg）group,normal saline blank control group and ifosfamide positive control group,each group of 8,continuous intraperitoneal administration for 10 days.Nude mice were observed during the administration of the spirit,reaction,activity,diet and toilet and other general situation.Andwere sacrificed after the lastinjection and tissue specimen was obtained.Tumor inhibition rate was calculated,The inhibitory effect of As₂O₃ was observed by flow cytometry.Detected the expression of Caspase3（RT-PCR）.The expression of Caspase3（immunocytochemistry）.The expression of p ERK（SP method）.Data processing and statistical analysis were performed.Results: 1.General condition,the As₂O₃ group and NS group had normal condition,normal activity,quick reaction,eating and drinking well,normal skin color,normal urine volume and body weight.Ifosfamide positive control group nude mice gradually decreased of the spirit,activity decreased,unresponsive,less food,diarrhea,weight loss and other cachexia performance.2.The tumor mass:The tumor mass of As₂O₃ group and ifosfamide group was lower than that of normal saline group（P <0.05）;the high dose As₂O₃ group and ifosfamide group was lower than other groups（P <0.05）.There was no significant difference between As₂O₃ high dose group and positive control group,and As₂O₃ middle and low dose groups.3.Apoptotic rate: The experimental group and the ifosfamide group showed a typical apoptotic peak.The apoptotic rate of each dose As₂O₃ group and ifosfamide group was higher than that of normal saline group（P <0.05）.The apoptotic rate of As₂O₃ group was also higher than that of ifosfamide group（P <0.05）.The apoptotic rate of different dose As₂O₃ group was different,the highdose group was the highest,the apoptotic rate of middle and low dose As₂O₃ group was not significantly different（P> 0.05）.4.The expression of caspase-3 gene: The As₂O₃ group was significantly higher than that in the saline group and ifosfamide group（P <0.05）.The high dose As₂O₃ group was higher than that in the middle and low dose group（P= 0.192）,but there was no significant difference between the two groups（P> 0.05）.5.p-ERK expression: The expression of p-ERK in As₂O₃ group and positive control group was lower than that in NS group,and the high dose As₂O₃ group was the lowest.There was significant difference between As₂O₃ low dose group and NS group（P <0.05）,but there was little difference between positive control group.Conclusion: 1.As₂O₃ could inhibit the proliferation of human uterine sarcoma transplanted subcutaneously in nude mice.Its mechanism is related to down-regulation of p-ERK,up-regulation of Caspase-3 gene expression and induction of apoptosis of tumor cells.2.the therapeutic dose of adverse reactions is les harmful,is a relatively safe and effective drugs,is expected to be used in addition to a variety of solid tumor treatment.