蟾毒灵诱导人胰腺癌细胞凋亡及其对TGF-β1表达的影响

Study on effect of apoptosis and tGF-β1 expression of human pancreatic cancer cell in nude mice with bufalin

目的研究蟾毒灵对裸鼠人胰腺癌的疗效及细胞凋亡的作用和机理。方法建立裸鼠人胰腺癌模型,随机分为对照组(NS)、5-氟尿嘧啶组(5-Fu)、蟾毒灵低剂量组(BuL)、蟾毒灵高剂量组(BuH)。分别腹腔注射生理盐水NS,20ml/kg、5-Fu24mg/kg、Bu1mg/kg、Bu1·5mg/kg。用药后第7天处死,计算肿瘤生长抑制率;TUNEL法检测瘤体凋亡指数;免疫组化S-P法检测P38、TGF-β1的表达。结果治疗后与NS组相比,各组瘤体体积均显著缩小(P<0·05)。其中Bu高剂量组瘤体体积明显<Bu低剂量组、5-Fu组(P<0·05)。Bu高剂量组凋亡指数高于其他各组(P<0·01);Bu高剂量组TGF-β1蛋白的表达明显低于其他各组(P<0·01)。结论蟾毒灵对胰腺癌的生长具有显著的抑制作用并能够诱导人胰腺癌细胞凋亡,抑制TGF-β1的表达。抑制TGF-β1的表达从而诱导胰腺癌细胞凋亡,是蟾毒灵治疗胰腺癌的部分机制。

Objective To explore the effect of apoptosis and TGF-β1 axpression of human pancreatic cancer cell in nude mice with Bufalin.Methods Human pancreatic cancer model in nude mice have been established and were divided into NS group randomly,5-Fu group,Bufalin(Bu) high dose group,Bufalin low dose group.Normal salin(NS)20ml/kg,5-Fu 24mg/kg,Bu1mg/kg,Bu 1.5mg/kg were injected via transperitoneal approach respectively.After treatment,on the seventh day,nude mice were sacrificed and then the volume of the tumor were compared among all groups.The cell apoptosis index was tested by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling technique(TUNEL),TGF-β1 was assayed by immunohistochemical technique(S-P method) and the its mechanism against cancer was discussed initially.Results The tumor volume and growth rate of Bufalin high dose group was significantly smaller than that of other groups(P<0.01).The apoptosis index of Bufalin high dose group was significantly higher than that of other groups(P<0.01),while its TGF-β1 expression was lower than that of other groups.Conclusion The suppressed expression of TGF-β1 could promote the apoptosis,which was one of the mechanism for Bufalin against pancreatic cancer.