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Effect of Jianpi Jiedu decoction to PTEN/ERK1 of athymic mice  with hepatocellular carcinoma

健脾解毒复方中药对裸鼠肝癌模型PTEN/ERK1的影响


目的:探讨肝癌裸鼠不同肝组织PTEN/ERK1的表达及健脾解毒复方中药对其的影响。方法:采用人肝细胞癌细胞株Bel-7402间接原位移植,造雄性肝癌裸鼠模型90只,造模24 h后随机分9组,即不同浓度复方中药A~G组,FT207化疗组,生理盐水组,10只裸鼠不造模作为正常对照组,给药每天1次,8周后处死裸鼠,免疫组化二步法检测肝组织、癌旁组织和癌组织PTEN/ERK1的表达情况。结果:荷瘤裸鼠肝脏PTEN蛋白表达强度正常肝组织>癌旁组织>癌组织。中药组B,D,E组PTEN在正常肝组织的表达高于生理盐水组、化疗组、正常照组,(P<0.05)。中药组D组PTEN在癌旁组织的表达高于生理盐水组,(P<0.05),中药组在癌组织中PTEN的表达高于生理盐水组和化疗组,(P<0.05)。荷瘤裸鼠肝脏ERK1蛋白表达强度癌组织>癌旁组织>肝组织,癌旁组织ERK1表达强度化疗组高于中药组和生理盐水组,癌组织ERK1表达强度生理盐水组和化疗组均高于中药C,D,E,G,F组。在癌组织中,PTEN和ERK1的表达呈负相关,(P<0.01)。结论:在肝癌的发生发展过程中PTEN的缺失或突变可能导致了ERK1的过度活化,健脾解毒复方中药可能对PTEN/ERK1有良性调节作用。

Objective: To research the effect of Jianpi Jiedu decoction  (JPJDT) to PTEN/ERK1 of athymic mice with hepatocellular carcinoma.  Method: N2 male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 90 athymic mice were distributed randomly into JPJDT groups: A, B, C, D, E, F, G, NS, FT each group had 10 athymic mice. Another 10 male BALB/c athymic mice without HCC was treated by NS as normal control (DZ). Group A to G were treated by intragastric administration with JPJDT that had been deliquated into 7 kinds of density for 8 wk. Group NS were were treated by intragastric administration with Sodium Chloride for 8 wk. Group FT were were treated by intragastric administration with FT207 (tegafur) for 8 wk . At last, athymic mice were sacrificed. PTEN/ERK1 was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry (PowerVisionTM two-step histostaining reagent).  Result: The expression intensity of PTEN:  The result showed that the intensity of PTEN in the normal hepatic tissue was the highest, and then latero-cancer tissue, the lowest was cancer tissue. In the normal hepatic tissue, the intensity of PTEN in Group B, D, E was higher than the Group NS, Group FT, Group DZ (P<0.05). In the latero-cancer tissue, the intensity of PTEN in Group D was higher than the Group NS (P<0.05). In the cancer tissue, the intensity of PTEN in Group JPJDT was higher than the Group NS and Group FT (P<0.05). The expression intensity of ERK1: The result showed that the intensity of PTEN in the cancer tissue was the highest, and then latero-cancer tissue, the lowest was normal hepatic tissue. In the latero-cancer tissue, the intensity of ERK1in Group FT was higher than the Group NS and Group JPJDT (P<0.05). In the cancer tissue, the intensity of PTEN in Group NS and Group FT was higher than the Group C, D, E, G, F (P<0.05). The correlation between PTEN and ERK1: The result showed that there was inverse correlation between the expression intensity of PTEN and ERK1 in the cancer tissue (P<0.01).  Conclusion: One of mechanism of antitumous effect of JPJDT maybe up-regulate anti-oncogene PTEN, restrain the signal way of ERK1, suppress the proliferation of hepatoma carcinoma cell. The carcinogenesis of primary hepatic carcinoma may exist the deletion of PTEN. Owing to low expression or deletion of PTEN in the cancer tissue, ERK1signal transduction pathway cannot be actively suppressed which was activated by carcinogenic factor. So hepatoma carcinoma cell multiplicated.