Changes of moleculars involved in PI3K/AKT pathway in emodin-induced apoptosis of human leukemia K562 cells in nude mice
10.3781/j.issn.1000-7431.2011.07.001
- Author:
Chun-Guang WANG
1
Author Information
1. Department of Oncology
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Emodin;
Gene expression;
K562 cells;
Leukemia, experimental;
Mice, inbred BALB C;
PI3K/AKT signal transduction pathway;
Xenograft model antitumor assays
- From:
Tumor
2011;31(7):573-579
- CountryChina
- Language:Chinese
-
Abstract:
Objective: 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. Emodininduced 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 FoxO 3a mRNAs and proteins, respectively. Results: The relative tumor volumes (V/V0) were significantly smaller in the low-, moderate- 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 FoxO 3a 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 FoxO 3a 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. Copyright© 2011 by TUMOR.
