Periplocin from Cortex periplocae inhibits cell growth and down-regulates survivin and c-myc expression in colon cancer in vitro and in vivo via beta-catenin/TCF signaling.
Periplocin from Cortex periplocae inhibits cell growth and down-regulates survivin and c-myc expression in colon cancer in vitro and in vivo via beta-catenin/TCF signaling.
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DOI：
10.3892/or_00000870
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发表时间：
2010-08
期刊：
影响因子：
4.2
通讯作者：
Lianmei Zhao;B. Shan;Yan-yan Du;Mingxia Wang;Lihua Liu;Feng-zhi Ren
中科院分区：
文献类型：
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作者：
Lianmei Zhao;B. Shan;Yan-yan Du;Mingxia Wang;Lihua Liu;Feng-zhi Ren
结肠癌和直肠癌是第三种最常见的癌症，约占所有与癌症相关的死亡人数的10%。虽然手术切除或放射治疗有可能治愈局部疾病，但目前晚期结肠癌预后较差。因此，需要开发一种新的有效的化疗药物来靶向关键途径，以诱导结肠癌细胞对死亡信号的应答。β-连环蛋白/TCF通路的失调在结直肠癌发生的早期活动中起着核心作用。本研究以人结肠癌SW480细胞为研究对象，研究香附多糖(CPP)对β-连环蛋白/TCF信号通路的影响。我们的研究结果表明，通过四甲基偶氮唑盐比色法检测CPP对细胞生长的抑制作用呈剂量和时间依赖性，通过流式细胞仪和透射电子显微镜检测CPP诱导细胞凋亡。此外，CPP处理的细胞的特征是在总细胞裂解物以及胞浆和核提取液中β-连环素蛋白的表达减少。这种表达降低了T细胞因子(Tcf)复合体与其特定DNA结合位点的结合活性。因此，下游元件Survivin和c-myc的蛋白表达下调。为了确定相关的确切抑制机制，有必要对CPP进行进一步的体内深入研究。综上所述，我们的数据表明，CPP通过多管齐下的策略来靶向β-连环蛋白/Tcf信号通路，从而在体内外诱导结肠癌细胞的凋亡和抑制生长。因此，CPP可能成为一种潜在的抗结肠癌药物。
Cancer of the colon and rectum is the third most commonly diagnosed cancer and accounts for approximately 10% of all cancer-related deaths. Although surgical resection or radiotherapy are potentially curative for localized disease, advanced colon cancer is currently associated with poor prognosis. Therefore, the development of a new and effective chemotherapeutic agent is required to target critical pathways to induce responsiveness of colon cancer cells to death signals. Dysregulation of the beta-catenin/TCF pathway plays a central role in early activities of colorectal carcinogenesis. In this study, human colon cancer SW480 cells were used to investigate the effect of CPP (periplocin from Cortex periplocae) on the modulation of the beta-catenin/TCF signaling pathway. Our research results showed that CPP caused a dose- and time-dependent inhibition of cell growth as assessed by MTT assay and an induction in apoptosis as measured by flow cytometry and transmission electron microscopy. Furthermore, the CPP- treated cells were characterized by a decreased expression of beta-catenin protein in the total cell lysates and cytosolic and nuclear extracts. This expression alleviates the binding activity of T-cell factor (Tcf) complexes to its specific DNA-binding sites. Thus, the protein expression of the downstream elements survivin and c-myc was down-regulated. To determine the precise inhibitory mechanisms involved, further in-depth in vivo studies of CPP are warranted. In conclusion, our data suggest that CPP wields a multi-prong strategy to target the beta-catenin/Tcf signaling pathway, leading to the induction of apoptosis and inhibition of growth of colon cancer cells in vitro and in vivo. Therefore, CPP may become a potential agent against colon cancer.