Inhibitorv effect of emodin on heterotransplanted human bladder cancer in nude mice and its mechanism / 中国医师杂志

ABSTRACT

Objective To investigate the inhibitory effect of emodin on hetertransplanted human bladder cancer in nude mice and explore its mechanism.Methods Heterotransplanted models of human bladder cancer cell line BIU87 cells in nude mice were established.The mice were randomly divided into 4 groups during the experimentblank control group,Z-VAD-FMK group,emodin group and emodin combined with Z-VAD-FMK group.The growth of tumors was observed and the growth curve was mapped.The nude mice were sacrificed 4 weeks later,the tumors were isolated and weighed.The pathological changes of tumor were observed after HE staining,the cells apoptosis were detected with flow cytometry,and the expression of AIF and Endo G were examined by reverse transcription PCR (RT-PCR) and Western blot.Results The tumor growth rate in emodin group was lower than that in the other three groups.The tumor quality in emodin group [(0.41 ± 0.05 ) g] and emodin combined with Z-VAD-FMK group [( 0.69 ±0.07)g]were lighter than that in the other two groups[(1.08 ±0.13,1.04 ±0.09)g,],and the differences were statistically significant( F =90.56,27.49,P ＜0.01 ).The quality difference in emodin group and emodin combined with Z-VAD-FMK group was statistically significant ( t =10.01,P ＜ 0.01 ).The apoptosis rate in emodin group [(42.71 ±2.69)％]was significantly higher than that in emodin combined with Z-VAD-FMK group[(34.38 ± 1.73)％] ( t =6.38,P ＜0.01 ).The expression of AIF and Endo G in emodin combined with Z-VAD-FMK group was significantly increased than other groups [( 1.65 ±0.12)vs(1.24±0.08),(0.51 ±0.07),(0.48 ±0.04);(2.12 ±0.16)vs(1.75 ±0.13),(0.57 ±0.06),(0.59±0.07);(2.42±0.13)vs(1.73 ±0.11),(0.78 ±0.07),(0.75 ±0.08);(3.13 ±0.25)vs(2.15± 0.18 ),(0.85 ± 0.09 ),(0.81 ± 0.14 )],and the differences were significant ( F =303.22,319.32,409.38,258.53,P ＜ 0.01 ).Conclusions Emodin could significantly inhibit the growth of hetertransplanted human bladder cancer in nude mice.The mechanism might be partly due to the expression increase of AIF and Endo G in bladder cancer cells,which might induce apoptosis through Caspase-independent pathway.