氯化镉对裸鼠皮下移植人肝癌SMMC-7721细胞的抑制作用及其对线粒体酶的影响

Inhibitory effects of cadmium chloride on SMMC-7721 cells in hepatocarcinoma transplanted nude mice and influence in mitochondrial enzymes

目的:研究氯化镉对裸鼠皮下移植人肝癌SMMC-7721细胞的抑制作用及对线粒体乳酸脱氢酶(LDH)、ATP酶活性的影响,阐明氯化镉抑制肿瘤生长的机制。方法:建立人肝癌裸鼠皮下荷瘤模型,分别腹腔注射生理盐水(阴性对照组)、5-氟尿嘧啶(阳性对照组)、氯化镉0.5、1.0和2.0mg.kg-1(氯化镉组),10d后测定荷瘤体积、脏器指数和血清ALT、AST水平及荷瘤组织线粒体LDH、ATP酶的活性。结果:与阳性对照组比较,氯化镉0.5、1.0和2.0mg.kg-1组肿瘤抑制率增加,但差异无统计学意义(P>0.05);各组脏器指数变化不明显,其中氯化镉各剂量组肾脏指数高于阳性对照组(P<0.05);与阴性对照组比较,氯化镉各剂量组ALT水平及LDH酶活性显著降低(P<0.05),0.5和1.0mg.kg-1组AST水平显著降低(P<0.05);1.0和2.0mg.kg-1组Ca2+-Mg2+-ATPase活性与阴性对照组比较差异具有统计学意义(P<0.05),0.5和2.0mg.kg-1组Na+-K+-ATPase活性与阳性对照组比较差异具有统计学意义(P<0.05)。结论:氯化镉可能干扰线粒体能量代谢,并通过线粒体途径抑制肿瘤生长。

Objective To study the inhibitory effects of cadmium chloride（CdCl2） on SMMC-7721 cells in hepatocarcinoma transplanted nude mice and influence in mitochondrial enzymes and clarify their mechanisms.Methods The hepatocarcinoma transplanted nude mouse model were established in vivo.The mice in negative control group were administered with sodium chloride,the mice in positive control group were administered with 25 mg·kg-1 5-Fu,and the mice in Cdcl2 groups were administered with 0.5,1.0,2.0 mg·kg-1 CdCl2,respectively.The anti-tumor effects of CdCl2,the changes of serum ALT and AST levels,the activities of LDH and ATPase in mitochondria were detected 10 d after administration.Results Compared with positive control group,the inhibitory rate of tumor tended to increase along with the elevating of CdCl2 dose,but there were no statistical significances（P0.05）.The organ indexes in all CdCl2 groups didn＇t change greatly,but the kidney organ indexes in CdCl2 groups were higher than that in positive control group（P0.05）.Compared with negative control group,the level of ALT and the activity of LDH in CdCl2 groups were significantly decreased（P0.05）,and the level of AST in 0.5 and 1.0 mg·kg-1 CdCl2 groups were also significantly decreased（P0.05）.The activities of Ca2＋-Mg2＋-ATPase in 1.0 and 2.0 mg·kg-1 CdCl2 groups were significantly increased compared with negative control group（P0.05）,the activities of Na＋-K＋-ATPase in 0.5 and 2.0 mg·kg-1 CdCl2 groups were significantly increased compared with positive control group（P0.05）.Conclusion CdCl2 may interfere the energy metabolism of mitochondria and inhibit the growth of the transplanted hepatocarcinoma through mitochondria way.