ANTI-TUMOR EFFECT OF ARSENIC TRIOXIDE ON SUBCUTANEOUSLY TRANSPLANTED HUMAN CERVICAL CARCINOMA IN NUDE MICE

Objective To study the anti-tumor effect of arsenic trioxide with different concentrations on subcutaneously transplanted human cervical carcinoma(HCC) cell(Hela cell line) in nude mice and their action and mechanism. Methods A tumor model of human HCC was created by subcutaneous inoculation of 4×106 Hela cells into nude mice.The mice were randomized to low-(1.0 mg/kg),medium-(2.5 mg/kg),and high-dose arsenic trioxide(5.0 mg/kg) group,saline group and DDP group.The mice in each group received intraperitoneal injection of the drug for 10 days,and were sacrificed 24 hours after the last injection and tissue specimen was obtained.Tumor inhibition rate was calculated,the apoptosis rate detected with flow cytometry,the relative expression of caspase-3 gene was determined with RT-PCR.Immunohistochemistry SP method was adopted to detect the expression of phosphorylated extra-cellular signal-regulated kinase(pERK). Results Compared with saline group,the mice in arsenic trioxide groups and DDP group showed significant inhibition in the growth of the transplanted tumor(F=39.14,P0.05).The apoptotic peak was observed in all three arsenic groups with the apoptosis rates being 17.89%,17.19% and 18.52% for the high-,medium-and low-dose groups,respectively.The expression of caspase-3 in arsenic groups was significantly higher than that of the saline group(F=8.76,q=3.06-5.81,P0.05),while the expression of pERK was lower. Conclusion Arsenic trioxide showed obvious inhibition on the growth of transplanted HCC cells.The inhibitory action is related to the up-regulation of caspase-3 expression which induces apoptosis,down-regulation of pERK expression and inhibition of MAPK signal transducting system.