表没食子儿茶素没食子酸酯对慢性粒细胞白血病模型小鼠的治疗作用及可能机制

The curative effect of EGCG on CML mice and its possible mechanisms

目的观察表没食子儿茶素没食子酸酯(EGCG)对慢性粒细胞白血病(CML)模型小鼠的治疗作用,并分析可能机制。方法将CML小鼠随机分为对照组及EGCG治疗组(EGCG组)。EGCG组小鼠接受EGCG治疗,具体为:EGCG15 mg/kg,腹腔注射,每周2次,共治疗4周。对照组接受等量的生理盐水腹腔注射。观察小鼠体重变化及肿瘤大小。采用免疫组化及Western bolt法检测并比较两组小鼠肿瘤组织中Bcr/abl融合基因蛋白(BCR-ABL)、肿瘤组织中含SH2结构域的蛋白质酪氨酸磷酸酶1(SHP-1)的表达。采用Western bolt法检测两组小鼠SHP-1、STAT3、半胱天冬酶-3(Caspse-3)、半胱天冬酶-6(Caspase-6)及半胱天冬酶-9(Caspase-9)的表达。结果治疗结束后,EGCG组小鼠体重显著高于对照组(P<0.05,且肿瘤重量显著低于对照组(P<0.05)。EGCG组小鼠肿瘤组织BCR-ABL表达量显著低于对照组(P<0.05)。EGCG组小鼠肿瘤组织内SHP-1表达量显著高于对照组(P<0.05)。EGCG组小鼠肿瘤组织内p-STAT3水平显著低于对照组小鼠(P<0.05)。EGCG组小鼠肿瘤组织内Caspase-3及Caspase-9水平显著高于对照组小鼠(P<0.05)。两组Caspase-6水平比较差异无统计学意义(P>0.05)。结论EGCG可抑制CML模型小鼠的肿瘤生长,该作用可能是通过激活SHP-1/STAT3信号通路实现的。

Objective To analyze the curative effect of EGCG on CML mice and its possible mechanisms.Methods CML mice were divided into 2 groups,Group A:EGCG treatment(15 mg/kg,intraperitoneal injection,4 weeks);Group B:saline control.Mouse body weight change and tumor weight were observed.The expression of Bcr/abl fusion gene protein(BCR-ABL)in the tumor tissues of the two groups of mice was detected and compared by immunohistochemistry and Western bolt method.Two groups of mouse tumor tissues containing SH2 domain protein tyrosine phosphatase 1(SHP-1),STAT3,caspase-3(Caspse-3),caspase-6(Caspase-6)and the expression of caspase-9(Caspase-9)was detected by Western bolt method.Results After experiment,Group A had a lower tumor weight,but a higher body weight than those of Group B,the difference was statistically significant(P<0.05).Group A mice had a lower levels of BCR-ABL in tumor than that of Group B mice(P<0.05).Group A mice had a higher levels of SHP-1 in tumor than that of Group B mice,the difference was statistically significant(P<0.05).Group A mice had a lower levels of p-STAT3 in tumor than that of Group B mice,the difference was statistically significant(P<0.05).Group A mice had higher levels of Caspase-3 and Caspase-9 in tumor than these of Group B mice,the difference was statistically significant(P<0.05).Conclusion EGCG can suppress tumor growth in vivo,which may though activating the SHP-1/STAT3signaling pathway.