Extract of Pleurotus pulmonarius suppresses liver cancer development and progression through inhibition of VEGF-induced PI3K/AKT signaling pathway.
Extract of Pleurotus pulmonarius suppresses liver cancer development and progression through inhibition of VEGF-induced PI3K/AKT signaling pathway.
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DOI：
10.1371/journal.pone.0034406
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cheung PC
中科院分区：
文献类型：
--
作者：
Xu W;Huang JJ;Cheung PC
肝癌或肝细胞癌是癌症相关死亡的主要原因之一。传统的化疗方法受到耐药性产生和各种副作用的限制。由于其无毒和强大的生物药理活性，蘑菇中的代谢产物在癌症治疗中受到了越来越多的关注。我们以前的研究已经证明了从平菇中提取的多糖-蛋白质复合体具有抗癌作用。本研究的目的是研究含有肺菇多糖-蛋白质复合体的热水提取物对肝癌细胞的抗癌作用的分子机制。我们的结果表明，肝癌细胞暴露于PP不仅能显着降低癌细胞的体外增殖和侵袭能力，而且能增强其对化疗药物顺铂的敏感性。口服和腹腔注射PP均能明显抑制BALB/c裸鼠移植瘤生长。PP在体内外对肝癌细胞的PI3K/AKT信号通路均有明显的抑制作用，AKT活性形式Myr-AKT的过表达可阻断PP对PI3K/AKT信号通路的抑制作用，抑制其增殖和侵袭。免疫印迹和ELISA法结果均显示PP处理的肝癌细胞血管内皮生长因子(VEGF)表达和分泌减少。加入重组人血管内皮生长因子可减弱PP对PI3K/AKT通路和肿瘤表型的抑制作用。我们的结果表明，PP在体内外通过抑制自分泌的PI3K/AKT信号通路来抑制肝癌细胞的增殖、侵袭和耐药。本研究提示PP在人肝癌治疗中具有潜在的治疗意义。
Liver cancer or hepatocellular carcinoma is one of the leading causes of cancer-related deaths. Conventional chemotherapies are limited by the development of drug resistance and various side effects. Because of its non-toxicity and potent biopharmacological activity, metabolites derived from mushrooms have received more attention in cancer therapy. Our previous studies have demonstrated the anticancer effects of polysaccharide-protein complexes derived from the Pleurotus mushrooms. The aim of this study was to investigate the underlying molecular mechanism of the anticancer activity of a hot water extract containing a polysaccharide-protein complex isolated from Pleurotus pulmonarius (PP) in liver cancer cells. Our results indicated that exposure of liver cancer cells to PP not only significantly reduced the in vitro cancer cell proliferation and invasion but also enhanced the drug-sensitivity to the chemotherapeutic drug Cisplatin. Both oral administration and intraperitoneal injection of PP significantly inhibited the tumor growth in xenograft BALB/c nude mice. PP triggered a marked suppression of the PI3K/AKT signaling pathway in liver cancer cells in vitro and in vivo, and overexpression of the constitutively active form of AKT, Myr-AKT, abrogated this effect and the inhibited proliferation and invasion by PP. Both western blot and ELISA results showed that PP-treated liver cancer cells had reduced expression and secretion of vascular endothelial growth factor (VEGF). Addition of recombinant human VEGF attenuated the inhibitory effects of PP on PI3K/AKT pathway and the cancer phenotypes. Our results demonstrated that PP suppressed the proliferation, invasion, and drug-resistance of liver cancer cells in vitro and in vivo, mediated by the inhibition of autocrine VEGF-induced PI3K/AKT signaling pathway. This study suggests the potential therapeutic implication of PP in the treatment of human liver cancer.
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影响因子：
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