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阻断肝癌衍生生长因子诱导人结直肠癌细胞凋亡。

Apoptosis of human colorectal carcinoma cells is induced by blocking hepatoma-derived growth factor.

机构信息

Department of Gastroenterology, Renmin Hospital, and Pathology Department, Wuhan University, 99# Zhi yang Road, 430060, Wuhan, Hubei, People's Republic of China.

出版信息

Med Oncol. 2010 Dec;27(4):1219-26. doi: 10.1007/s12032-009-9362-1. Epub 2009 Nov 19.

Abstract

Hepatoma-derived growth factor (HDGF) is a novel multifunctional growth factor that elicits pleiotropic effects on biological processes such as lung remodeling and renal development. Recent studies demonstrated that HDGF is related to tumor proliferation, invasion, angiogenesis, and apoptosis. However, the molecular mechanism of HDGF's involvement in apoptosis remains to be clarified. In this study, we first analyze the role of HDGF in colorectal carcinoma (CRC) progression by immunohistochemistry. Then we used small interference RNA (HDGF-siRNA) to block HDGF and assessed its effect on inducing apoptosis of CRC loVo cells. Apoptosis was detected using flow cytometry (FCM), DNA ladder analysis, and Hoechst 33258 staining. In addition, the expression levels of some apoptosis-related proteins were examined by western blot. The result showed that HDGF expression gradually increased in the colorectal carcinogenesis process. Further studies demonstrated that knock-down of HDGF can down-regulate the survivin, activate the mitochondrial pathway, and induce apoptosis in loVo cells. These findings suggest that HDGF is involved in colorectal carcinogenesis process. Further blocking HDGF exhibits potent pro-apoptotic properties in colon cancer cells. Thus, HDGF might be a potential therapeutic target for human colorectal cancer. These findings may have major implications in the treatment of colorectal cancer.

摘要

肝癌衍生生长因子(HDGF)是一种新型多功能生长因子,对肺重塑和肾脏发育等生物学过程具有多种效应。最近的研究表明,HDGF与肿瘤增殖、侵袭、血管生成和凋亡有关。然而,HDGF 参与凋亡的分子机制仍有待阐明。在本研究中,我们首先通过免疫组织化学分析 HDGF 在结直肠癌(CRC)进展中的作用。然后,我们使用小干扰 RNA(HDGF-siRNA)阻断 HDGF,并评估其对诱导 CRC loVo 细胞凋亡的影响。通过流式细胞术(FCM)、DNA 梯状分析和 Hoechst 33258 染色检测细胞凋亡。此外,通过 Western blot 检测一些凋亡相关蛋白的表达水平。结果表明,HDGF 的表达在结直肠癌发生过程中逐渐增加。进一步的研究表明,敲低 HDGF 可以下调生存素,激活线粒体途径,并诱导 loVo 细胞凋亡。这些发现表明 HDGF 参与了结直肠癌的发生过程。进一步阻断 HDGF 在结肠癌细胞中表现出很强的促凋亡作用。因此,HDGF 可能是人类结直肠癌的潜在治疗靶点。这些发现可能对结直肠癌的治疗具有重要意义。

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