TGF-β_1对胰腺癌细胞生长的影响及TGF-β_1、Smad4和p21^(waf1)在胰腺癌组织中的表达

Effect of transforming growth factor β_1 on the growth regulatory of human pancreas carcinoma cell and expression of TGF-β_1,Smad4,p21^(waf1) in human pancreas carcinoma tissue

目的 观察TGF β1通路中TGF β1、Smad4及p2 1waf1的表达关系及它们在胰腺癌中的可能作用机制。方法 用四甲基偶氮唑蓝 (MTT)法观察TGF β1对人胰腺癌细胞系JF 30 5增殖作用的影响 ;通过免疫组化技术检测 4 5份人石蜡包埋胰腺癌组织以及 2 0份胰腺良性病变中TGF β1、Smad4和p2 1waf1蛋白表达。结果 TGF β1早期抑制胰腺癌细胞系JF 30 5增殖 ,作用与剂量成正比。 4 5份胰腺癌组织中TGF β1、Smad4和p2 1waf1阳性率分别为 6 6 .6 7%( 30 / 4 5 )、6 0 % ( 2 7/ 4 5 )和 37.78% ( 17/ 4 5 ) ,与良性对照组阳性率相比差异显著 ,TGF β1与肿瘤转移相关 (P <0 .0 5 ) ,Smad4与肿瘤分化程度相关 (P <0 .0 5 )。结论 外源TGF β1早期可以显著抑制胰腺癌细胞系JF 30 5的生长 ;胰腺癌组织中Smad4表达降低 ,其下游基因p2 1waf1基因表达随之降低 ,二者有相关性 ,但TGF β1表达增高。

Objective To observe the effect of TGF-β 1 on cell proliferation of human pancreatic cancer cell line JF 305 and to study the expression of TGF β 1,Smad4, p21 waf1 in the TGF β 1 pathway and their relationship and the possible mechanisms by which they effect pancreatic carcinoma. Methods The MTT method was used to study the effect of TGF β 1 on the JF 305 cell proliferation. The immunohistochemistry was used to detect the expression of TGF β 1,Smad4, p21 waf1 in 45 cases of pancreatic cancer and 20 cases of benignant disease of pancreas.Results The growth of JF 305 was inhibited by TGF β 1 in the earlier period and the inhibitory rates for growth of JF 305 was positively correlated with the dose of TGF β 1.The positive rates of TGF β 1,Smad4, p21 waf1 in 45 cases of pancreatic cancer tissue was 66.67%(30/45),60%(27/45)and 37.78%(17/45) respectively, and had significant different with that of controls.The expression of TGF β 1 was closely related with cancer cells metastasis(P<0.05) and the expression of Smad4 was closely related with cancer cells differentiation.Conclusion TGF β 1 inhibits the growth of human pancreatic cancer cell line JF 305 in the earlier period. The expression of Smad4 in pancreatic cancer tissue significantly decrease and the expression of p21 waf1,the down stream gene of Smad4, is also decreased.There is a relationship between the expression of Smad4 and p21 waf1,but the expression of TGF β 1 are increased.