大豆染料木素抑制小鼠结肠肿瘤发生过程中PPAR-γ的作用和机制

ROLE OF PPAR-γ DURING THE PROCESS OF COLON CANCER INHIBITION BY GENISTEIN IN MICE

目的研究染料木素(Genistein)抑制小鼠结肠肿瘤发生过程中,过氧化物酶增殖物激活受体(PPAR-γ的作用和机制。方法用DSS/AOM法诱导雌性KM小鼠结肠肿瘤发生,小鼠共30只,分成正常对照组(normal,N)、结肠肿瘤诱导组(DSS/AOM)和日粮+Genistein(450mg/kg)的结肠肿瘤诱导组(DSS/AOM+Gen)三组,每组10只。分析小鼠结肠肿瘤的发生情况和健康状况,用Western-blot测定小鼠结肠组织相关蛋白的表达变化。结果 Genistein的添加明显降低了小鼠结肠肿瘤发生率,改善了结肠组织结构。结肠肿瘤小鼠PPARγ及PAT家族蛋白,包括Perilipin、TIP-47和ADRP等蛋白的表达显著提高,肿瘤抑制因子FOXO3a蛋白的表达显著降低(P<0.05),Genistein的添加对上述蛋白的表达起到了显著的逆转作用(P<0.05)。结论 PPARγ蛋白在结肠肿瘤中过表达,而Genistein的添加,抑制了其表达,从而进一步抑制了PAT家族蛋白的表达,使LDs积累减少,FOXO3a蛋白的表达活性升高,最终抑制结肠肿瘤的发生发展。

Objective To investigate the role of peroxisome proliferators-activated receptor gamma (PPAR-γ) in colon cancer inhibition by genistein in mice. Methods Colon cancer was induced by DSS/AOM method in female KM mice. Thirty mice were divided into normal control group (Normal, N), colon cancer induction group (DSS/AOM) and colon cancer induction group with 450mg/kg of genistein in diets (DSS/AOM+Genistein450mg/kg)(n=10). The tumorigenicity and physical conditions of mice were analyzed. The protein expressions were determined by Western-blot. Results Genistein decreased the tumorigenicity and improved the structure of colon in mice significantly. The expressions of PPAR-γ and PAT family proteins including perilipin, TIP-47 and ADRP were significantly increased in mice with colon cancer (P<0.05), while the expression of tumor suppressor FOXO3a was significantly decreased (P<0.05). The addition of genistein could reverse the changes of these proteins expression significantly (P<0.05). Conclusion PPAR-γ and PAT proteins are over-expressed in colon cancer, which can be reversed by genistein and followed by decreased LDs accumulation and increased FOXO3a. This results in the inhibition of colon cancer.