Anti-tumor effects of proteoglycan from Phellinus linteus by immunomodulating and inhibiting Reg IV/EGFR/Akt signaling pathway in colorectal carcinoma

Anti-tumor effects of proteoglycan from Phellinus linteus by immunomodulating and inhibiting Reg IV/EGFR/Akt signaling pathway in colorectal carcinoma
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DOI:
10.1016/j.ijbiomac.2011.01.014
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发表时间:
2011-04-01
影响因子:
8.2
通讯作者:
Hu, Gui-Yan
Hu, Gui-Yan
中科院分区:
化学1区
文献类型:
--
作者:
Li, You-Gui;Ji, Dong-Feng;Hu, Gui-Yan

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已报道从马齿菌中纯化的蛋白多糖(P1)具有抗疾病活性。本研究的目的是探讨P1对人癌细胞的抗肿瘤作用及其可能的机制。细胞抑制实验表明,P1对HepG 2、HT-29、NCI-H 460和MCF-7人结肠癌细胞均有抑制增殖作用,尤其对HT-29细胞有明显的抑制作用。当用P1(100 mg/kg)处理HT-29荷瘤小鼠时,脾脏和胸腺重量相对增加,血浆pIgR和伊加水平显著升高,并且通过ELISA测量的血浆PGE 2、Reg IV、EGFR和Akt浓度显著降低。RT-PCR分析表明,P1诱导的HT-29细胞凋亡似乎与Reg IV和EGFR表达水平的降低有关。这些结果表明,P1可能有两个潜在的作用,在治疗癌症,它作为一个免疫增强剂,部分通过保护T细胞逃避PGE 2的攻击和增强粘膜伊加反应,并作为一个直接的抑制剂,通过破坏Reg IV/EGFR/Akt信号通路。(C)2011爱思唯尔有限公司版权所有。
Proteoglycan (P1) purified from Phellinus linteus has been reported to have anti-disease activities. The objectives of our research were to determine the anti-tumor effect and possible mechanisms of P1 on human cancer cells. Cell inhibition assay showed that P1 has an antiproliferative effect on HepG2, HT-29, NCI-H 460 and MCF-7 human colon cancer cells, especially it was very effective in inhibiting HT-29 cells. When HT-29-bearing mice were treated with P1(100 mg/kg), there was relative increase in spleen and thymus weights, the plasmatic pIgR and IgA levels were significantly increased, also there was a notable decrease in plasmatic PGE2, Reg IV, EGFR and Akt concentrations measured by ELISA. RT-PCR analysis suggested that P1-induced HT-29 apoptosis appeared to be associated with a decrease in the levels of expression of Reg IV and EGFR. These results suggest that P1 might have two potential roles in treating cancer; it acts as an immunopotentiator partly through protecting T cells from escaping PGE2 attack and enhancing the mucosal IgA response, and as a direct inhibitor by disrupting the Reg IV/EGFR/Akt signaling pathway. (C) 2011 Elsevier B.V. All rights reserved.