bcl-2基因表达在genistein抑制裸鼠肝癌生长中的作用

Role of bcl-2 gene expression in inhabition of hepatocellular carcinoma by genistein in nude mice

目的:探讨bcl-2基因表达变化在genistein治疗裸鼠移植人肝癌中的作用。方法:以裸鼠移植人肝癌为对照,对照组腹腔注入含0.04%DMSO RPMI-1640培养基0.05 L/kg,genistein治疗组腹腔注入genistein 1mg kg-1·d-1,3周后观察肝癌增长情况,并应用同位素试剂盒检测肝癌组织IP3含量,RT-PCR分析癌组织bcl-2 mRNA表达,Western blotting分析肝癌组织Bcl-2蛋白表达。结果:治疗组肝癌体积和重量均显著低于对照组[体积:(42.7±27.8)mm3vs(52.3±26.5)mm3;重量:(42.7±27.8)mgvs(91.3±31.4)mg],IP3含量显著低于对照组[(13.4±1.4)nmol/g proteinvs(35.3±6.6)nmol/g protein],bcl-2 mRNA表达显著低于对照组[RI(灰度与面积之积的相对强度)0.48±0.02vs0.56±0.15],P<0.01,Bcl-2蛋白表达显著低于对照组[RI(灰度与面积之积的相对强度)1.69±0.52vs1.37±0.48]。结论:Genistein能减少IP3生成,下调肝癌组织bcl-2基因表达,抑制裸鼠移植肝癌的生长。

AIM ： To probe into the role of 1,4, 5 - trisphosphate inositol （ IP3 ） and bcl - 2 gene expression in inhibiting hepatocellular carcinoma of nude mice by genistein. METHODS ： Animals with hepatocellular carcinoma were treated with genistein 1 mg · kg^-1· d^-1 （ip） for 3 weeks. The volume and weight of tumaor were measured. IP3, bcl -2 mRNA, Bcl- 2 protein were assayed by IP3 - [^3H] Birtrak assay, RT -PCR, Western blotting, respectively. RE- SULTS： The tumor volume and weight of animals treated with genistein were lower than those in control （42.7mm^3 ± 27. 8mm^3 vs 52. 3mm^3 ±26. 5mm^3, 42. 7mg ±27. 8 mg vs 91.3mg ±31.4 mg）. IP3 content was lower than that in control [ （ 13.4 ± 1.4）nmol/g protein vs （35.3 ±6. 6） nmol/g protein], bcl-2 mRNA expression was lower in group treated with genistein than that in control （RI which was the gray degree multiply area of bcl-2 / the gray degree multiply area of β - actin 0. 48 ±0. 02 vs 0. 56 ±0. 15 ）. Bcl - 2 protein expression was lower in group treated with genistein than that in control （ RI 1.69 ± 0. 52 vs 1.37 ± 0. 48）. CONCLUSION ： Genistein inhibits growth of transplanted hepatocellular carci- noma in nude mouse liver by reducing IP3 production and down - regulating bcl -2 gene expression.