The in vivo apoptotic effect of interferon alfa-2b on rat preneoplastic liver involves Bax protein
The in vivo apoptotic effect of interferon alfa-2b on rat preneoplastic liver involves Bax protein
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DOI：
10.1053/jhep.2002.32099
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发表时间：
2002-04-01
期刊：
影响因子：
13.5
通讯作者：
Carrillo, MC
中科院分区：
文献类型：
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作者：
Alvarez, M;Cerliani, JP;Carrillo, MC
为了确定干扰素α（IFN-α）是否能预防极早期癌细胞的体内肿瘤发生，我们评估了IFN-α 2b对大鼠癌前病变的作用。将动物分为6组：进行2相模型（二乙基亚硝胺[DEN]加2-乙酰氨基芴[2-AAF]）的癌前病变。发育（组1），在2个阶段期间用IFN-α 2b处理（组2），仅在DEN起始期间（组3），仅在施用2-AAF期间（组4），仅经历起始阶段（组5），并在此期间用IFN-α 2b处理（组6）。胎盘型大鼠谷胱甘肽S-转移酶（rGST-P）阳性病灶/肝脏的数量和病灶占肝脏的百分比在第2、3和6组中显著降低，但在第4组中未降低。用IFN-α 2b处理的大鼠在改变的肝灶（AHF）中显示出较高的凋亡指数（AI）。在这些动物中，肝裂解物中的p53和Bax蛋白水平显著增加。同样，线粒体组分中抗凋亡蛋白Bcl-2和Bcl-x（L）的水平降低。最后，Bax蛋白水平的增加被定位在线粒体中。在接受IFN-α 2b的大鼠中，至少在DEN期（组2、3和6），线粒体Bax表达在组4中没有增加。总之，在起始阶段接受IFN-α 2b的大鼠中的癌前肝细胞经历程序性细胞死亡，这是Bax蛋白的量显著增加并易位至线粒体的主要结果。
To determine whether interferon alfa (IFN-alpha) prevents in vivo oncogenesis in very-early-stage cancer cells, we evaluated the action of IFN-alpha2b over preneoplastic foci in rats. Animals were divided into 6 groups: subjected to a 2-phase model (diethylnitrosamine [DEN] plus 2-acetylaminofluorene [2-AAF]) of preneoplasia. development (group 1), treated with IFN-alpha2b during the 2 phases (group 2), only during initiation with DEN (group 3), only during administration of 2-AAF (group 4), subjected only to an initiation stage (group 5), and treated with IFN-alpha2b during this period (group 6). The numbers of placental form of rat glutathione S-transferase (rGST-P)-positive foci per liver and the foci as percentage of liver were significantly reduced in groups 2, 3, and 6 but not in group 4. Rats treated with IFN-a2b showed a higher apoptotic index (AI) in altered hepatic foci (AHF). Levels of p53 and Bax protein in liver lysates were significantly increased in those animals. Similarly, levels of antiapoptotic proteins Bcl-2 and Bcl-x(L) in mitochondrial fraction were decreased. Finally, increased levels of Bax protein were localized in the mitochondria. of rats that received IFN-a2b, at least during the DEN phase (groups 2, 3, and 6), whereas mitochondrial Bax expression was not increased in group 4. In conclusion, the preneoplastic hepatocytes in rats that received IFN-alpha2b during the initiation stage undergo programmed cell death as a primary result of a significant increase in the amount and translocation to the mitochondria of Bax protein.