健脾解毒中药延长肝癌裸鼠带瘤生存时间及对PTEN/FAK的影响

目的探讨健脾解毒方提高裸鼠人肝癌模型的"带瘤生存"作用和对PTEN、FAK的影响。方法 40只裸鼠随机分为4组,每组10只,其中3组制作裸鼠人肝癌模型,分别给予健脾解毒方、生理盐水、替加氟(FT-207)灌胃,每天1次,持续71 d;第4组不造模作空白对照,每天给予生理盐水。实验过程中记录裸鼠生存时间和体质量,免疫组化SP法检测各组肝组织和癌组织PTEN、黏附斑激酶(FAK)的表达,IPP6.0分析平均光密度。结果生存分析表明健脾解毒方组裸鼠累积生存率显著高于其余各组(P<0.05或0.01);健脾解毒方组体质量减轻率显著低于其余各组(P<0.05或0.01);累积生存率和体质量减轻率FT-207组最差(P均<0.05);各组肿瘤体积比较无显著性差异(P均>0.05);PTEN在肝组织中的表达水平(平均光密度)显著高于癌组织(P<0.01);肝癌模型肝组织中PTEN表达水平明显低于空白组(P<0.05或0.01);FT-207组肝组织和癌组织中PTEN表达水平明显低于健脾解毒方组和生理盐水组(P<0.05或0.01);FAK在各组肝组织中的表达水平显著高于癌组织(P<0.01);健脾解毒方组肝组织中FAK表达水平显著高于其余各组(P均<0.01),癌组织中FAK表达水平显著低于其余各组(P均<0.01)。结论健脾解毒方能延长荷瘤鼠的带瘤生存时间,延缓体质量下降,其作用可能与健脾解毒方能良性调节PTEN、FAK的表达有关。

Effect of invigorating spleen and detoxication decoction on survival of HCC-bearing nude mice and PTEN/FAK

Objective It is to approach the effect of invigorating spleen and detoxication decoction(ISD) in improving survival of hepatocellular carcinoma-bearing nude mice and its influence to phosphatase and tensin homolog and focal adhesion kinase(PTEN/ FAK).Methods Forty male nude mice were divided into 4 groups randomly.3 groups were implanted human HCC tissues in liver,the animals were treated by ISD,saline and Tegafur(FT-207) respectively once a day for 10 weeks.Nude mice in another group without HCC were just treated by saline at the same time.Survival time and body weight of all these mice were recorded,PTEN/FAK in liver and cancer tissues was detected by immunohistochemical method,and expression intensity(The average optical density,AOD) of PTEN/FAK was analyzed by Image-pro plus 6.0.Results Survival analysis indicated that cumulative survival rate of nude mice treated by ISD was higher than the others(P<0.01 or 0.05).Weight loss rate of mice treated by ISD was the lowest(P<0.01 or 0.05).Survival rate and weight loss rate in mice treated by FT-207 was the worst(P<0.01).The expression of PTEN in liver tissues was higher than that in cancer tissues(P<0.01).The expression of PTEN in liver tissues of HCC models was lower than that in liver tissue of mice without HCC(P<0.01 or 0.05).The expression of PTEN in liver tissues and cancer tissues of mice treated by FT-207 was lower than mice treated by ISD and saline(P<0.01 or 0.05).The expression of FAK in liver tissues of mice treated by ISD was higher and in cancer tissues of it was lower than the others(P<0.01 or 0.05).Conclusion Mechanism of ISD prolonging survival time of HCC-bearing nude mice might be related with reducing weight loss and benign regulating PTEN/FAK.