中文摘要：

目的：观察大黄素作用后裸鼠体内白血病K562细胞P13K／AKT信号通路的分子变化，以探讨大黄素是否依赖P13K／AKT信号通路参与K562细胞凋亡发生。方法：建立裸鼠K562细胞皮下移植瘤模型，腹腔连续给药12d后，处死裸鼠，称取瘤体质量，计算抑瘤率。采用HE染色和透射电子显微镜观察肿瘤细胞的凋亡情况。应用RT—PCR法检测肿瘤组织中P13K、AKT和Fox03a的mRNA表达水平。蛋白质印迹法检测肿瘤组织中P13K、AKT和Fox03a蛋白的表达水平。结果：低、中、高剂量组大黄素作用后肿瘤相对体积（刃形）分别为8．90±0．24、5．62±0．17和2．06±0．31，与0．9％氯化钠溶液对照组（V／vo为11．83±0．47）相比，大黄素处理组的肿瘤体积明显缩小，差异具有统计学意义（P〈O．01）。光学显微镜和电子显微镜观察发现，大黄素能够诱导K562细胞发生明显的凋亡。I盯一PCR结果表明，不同剂量的大黄素能够引起P13K和AKTrnRNA的表达下调，而Fox03amRNA表达上调，且有剂量依赖性。蛋白质印迹法结果表明，大黄素处理组移植瘤组织中P13K、AKT蛋白表达水平明显降低，而Fox03a蛋白水平明显升高。结论：大黄素能够明显抑制人白血病K562细胞裸鼠移植瘤的生长，其机制可能与其抑制P13K/AKT信号转导通路有关。

英文摘要：

To observe emodin-induced molecular changes in PI3K/AKT signaling pathway in human leukemia K562 cells transplanted into BALB/c nude mice, and to explore whether emodin induces the apoptosis of K562 cells through PI3K/AKT signaling pathway. Methods： The subcutaneously transplanted tumor model of human K562 cells in nude mice was established. After continuously intraperitoneal injection with different doses of emodin for 12 d, the mice were sacrificed. Then the tumor weight and volume were measured, and the tumor inhibition rate was calculated. Emodin- induced apoptotic morphological changes of K562 cells were detected by HE stain and scanning electron microscopy. RT-PCR and Western blotting were used to detect the expressions of PI3K, AKT and FoxO3a mRNAs and proteins, respectively. Results： The relative tumor volumes （V/Vo） were significantly smaller in the lowmoderate and high-dose emodin-treated groups （8.90~0.24, 5.62_＋0.17 and 2.06_＋0.31, respectively） than that in the untreated group （11.83＋0.47; P〈0.01）. Significant apoptosis of K562 cells was found in emodin-treated groups under a light microscope and an electron microscope. RT-PCR revealed down-regulation of PI3K and AKT mRNAs expression and up-regulation of FoxO3a mRNA expression induced by different concentrations of emodin in a dose-dependent manner. Western blotting analysis showed that the expression levels of PI3K and AKT proteins were markedly decreased and the expression level of FoxO3a protein was significantly elevated in xenografted tumors treated with emodin. Conclusion： Emodin can significantly inhibit the growth of K562 cell xenografts in nude mice. The underlying mechanism may be associated with inhibition of PI3K/AKT signaling pathway.