期刊
ONCOTARGET
卷 8, 期 49, 页码 86693-86709出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.21411
关键词
beta-glucan; breast cancer; estrogen receptor positive; proliferation; apoptosis
资金
- National Key R&D Program of China [2016YFD0400202]
- National Natural Science Foundation of China [21574102, 21274114, 20874078]
- New Century Excellent Talents Program of Education Ministry of China [NCET-13-0442]
- Major Program of National Natural Science Foundation of China [21334005]
- Yellow Crane Talent Program of Wuhan City (China)
Breast cancer is now the most common cancer in worldwide women, and novel interventions are needed to overcome the resistance occurring in the estrogen-targeted endocrine therapy. Herein, we demonstrate that the beta-glucan from Lentinus edodes (LNT) exhibited a profound inhibition ratio of similar to 53% against estrogen receptor positive (ER+) MCF-7 tumor growth in nude mice similar to the positive control of cisplatin. Immunohistochemistry images showed that LNT evidently suppressed cell proliferation and promoted apoptosis in MCF-7 tumor tissues. The Western blotting analysis indicated that LNT up-regulated the tumor suppressor p53, phosphorylated extracellular signal-regulated kinase1/2 (p-ERK1/2), cleaved-Caspase 3 and poly [ ADP (ribose)] polymerase 1 (PARP 1) protein levels, and reduced the expression of mouse double minute 2 (MDM2), telomerase reverse transcriptase (TERT), nuclear factor-kappa B (NF-kappa B) p65, B-cell lymphoma-2 (Bcl-2), estrogen receptor alpha (ER alpha), etc. in tumor tissues. Moreover, LNT significantly suppressed phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt) and mammalian target of rapamycin (mTOR) protein levels. It was thus proposed that LNT inhibited MCF-7 tumor growth through suppressing cell proliferation and enhancing apoptosis possibly via multiple pathways such as PI3K/Akt/mTOR, NF-kappa B-, ERK-, ERa-, caspase-and p53-dependent pathways. Interestingly, the cell viability assay, siRNA transfection, Western blotting and flow cytometric analysis suggested that LNT targeted p53/ERa to only suppress cell proliferation via cell cycle arrest at G2/M phase without apoptosis in vitro. The big difference between in vivo and in vitro data suggested that the immune responses triggered by the polysaccharide should mainly contribute to the apoptotic effect in vivo. Overall, this work provides a novel strategy to treat ER+ breast cancers by using a naturally occurring beta-glucan from mushrooms.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据