摘要
背景:乳腺癌死亡率在世界范围内一直稳定或下降,近年来其发病率和复发率在全球范围内急剧上升。 目的:探讨GRP78在乳腺癌发生发展中的临床病理意义和潜在作用。探讨新异甘草素(NISL)对乳腺癌的治疗作用及其机制。 方法:采用乳腺癌组织微阵列(TMAs)免疫组织化学方法(IHC)检测GRP78,并分析GRP78水平与临床病理因素及预后的关系。通过MTT测定,病灶形成测定,基质胶侵袭测定和小鼠异种移植测定验证了GRP78对乳腺癌的功能性作用。通过MTT测定,细胞凋亡测定和小鼠异种移植测定来测试NISL的作用。利用LigandFit算法,ATP酶活性测定,蛋白印迹和免疫组织化学实验来发现NSIL作用的潜在机制。 结果:GRP78在乳腺癌细胞系和组织中高度表达。此外,GRP78的高表达与不良结果和远处转移相关。功能实验表明,GRP78促进了乳腺癌的体外和体内增殖和侵袭。 NISL通过与GRP78直接结合来调节β-连环蛋白途径来抑制乳腺癌细胞增殖并诱导细胞凋亡。
关键词: 新异甘草素,GRP78,β-连环蛋白信号传导,乳腺癌,进展,生物标志物。
图形摘要
Current Cancer Drug Targets
Title:Neoisoliquiritigenin Inhibits Tumor Progression by Targeting GRP78-β- catenin Signaling in Breast Cancer
Volume: 18 Issue: 4
关键词: 新异甘草素,GRP78,β-连环蛋白信号传导,乳腺癌,进展,生物标志物。
摘要: Background: Breast cancer mortality has been stable or decreasing in the world, its incidence and recurrence rates have sharply risen worldwide in the recent years.
Objective: To investigate the clinicopathological significance and potential function of GRP78 in the development and progression of breast cancer. To explore the effects of neoisoliquiritigenin (NISL) in breast cancer and the underlying mechanism.
Method: GRP78 was detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs), and the association between GRP78 levels and clinicopathological factors and prognosis was analyzed. The functional effects of GRP78 on breast cancer were validated by an MTT assay, foci formation assay, Matrigel invasion assay and mouse xenograft assay. The effects of NISL were tested by an MTT assay, apoptosis assay and mouse xenograft assay. A LigandFit algorithm, ATPase activity assay, western blot and IHC assay were used to discover the underlying mechanism of the effects of NSIL.
Results: GRP78 was highly expressed in breast cancer cell lines and tissues. In addition, high expression of GRP78 was correlated to poor outcomes and distant metastasis. Functional experiments showed that GRP78 promoted breast cancer proliferation and invasion in vitro and in vivo. NISL inhibited cell proliferation and induced cell apoptosis in breast cancer by directly binding to GRP78 to regulate the β-catenin pathway.
Conclusion: Taken together, these results highlighted the significance of GRP78 in breast cancer development and suggested NISL as a natural candidate to inhibit breast cancer by targeting GRP78 and β-catenin signaling.
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Cite this article as:
Neoisoliquiritigenin Inhibits Tumor Progression by Targeting GRP78-β- catenin Signaling in Breast Cancer, Current Cancer Drug Targets 2018; 18 (4) . https://dx.doi.org/10.2174/1568009617666170914155355
DOI https://dx.doi.org/10.2174/1568009617666170914155355 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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