生物谷報(bào)道：法國(guó)國(guó)家科研中心的研究人員日前報(bào)告說(shuō),，他們此前為治療艾滋病而合成的一種分子能夠阻斷腫瘤細(xì)胞的生長(zhǎng),，并破壞其周圍血管的生成,。這一研究為腫瘤治療提供了新思路。
科研人員早在1998年就合成了這種名為HB-19的分子,，當(dāng)時(shí)是為了研究艾滋病的療法,，不過(guò)最近他們發(fā)現(xiàn)，HB-19分子對(duì)于清除腫瘤細(xì)胞表面的核仁素具有特殊功效,。
核仁素是真核細(xì)胞核仁中的一種蛋白質(zhì),，它直接或間接參與細(xì)胞的繁殖和生長(zhǎng)，具有十分重要的作用,。
負(fù)責(zé)這項(xiàng)研究的阿拉·霍瓦尼西安表示,，癌癥的出現(xiàn)需要兩個(gè)因素：其一是腫瘤細(xì)胞增殖，其二是為腫瘤細(xì)胞提供營(yíng)養(yǎng)的血管,，而這兩者的生長(zhǎng)都與核仁素有關(guān),。HB-19分子可與核仁素結(jié)合，進(jìn)入細(xì)胞質(zhì)中,，核仁素隨后會(huì)發(fā)生分解,，從而阻斷癌癥發(fā)生的過(guò)程。
為了證明這一方法的有效性,，研究人員將人的腫瘤細(xì)胞植入實(shí)驗(yàn)鼠體內(nèi),，然后給它注射了含有HB-19分子的針劑。實(shí)驗(yàn)結(jié)果顯示,，腫瘤的生長(zhǎng)得到了顯著抑制,，在一些比較好的情況下，腫瘤細(xì)胞甚至被全部殺死,。
這一成果發(fā)表在新一期美國(guó)《公共科學(xué)圖書館·綜合》（PLoS ONE）雜志上,，并有望于2009年進(jìn)入臨床試驗(yàn)階段。（生物谷www.bioon.com）
生物谷推薦原始出處：
PLoS ONE,，doi:10.1371/journal.pone.0002518,，Damien Destouches，Ara G. Hovanessian
Suppression of Tumor Growth and Angiogenesis by a Specific Antagonist of the Cell-Surface Expressed Nucleolin
Damien Destouches1#, Diala El Khoury2#, Yamina Hamma-Kourbali1, Bernard Krust2, Patricia Albanese1, Panagiotis Katsoris3, Gilles Guichard4, Jean Paul Briand4, José Courty1, Ara G. Hovanessian2*
1 CNRS UMR 7149, Université Paris-Est, Créteil, France2 CNRS UPR 2228, Université Paris Descartes, Paris, France3 Laboratory of Molecular Pharmacology, University of Patras, Patras, Greece4 CNRS UPR 9021, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France
Abstract
Background
Emerging evidences suggest that nucleolin expressed on the cell surface is implicated in growth of tumor cells and angiogenesis. Nucleolin is one of the major proteins of the nucleolus, but it is also expressed on the cell surface where is serves as a binding protein for variety of ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis.
Methodology/Principal Findings
By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, here we show that the growth of tumor cells and angiogenesis are suppressed in various in vitro and in vivo experimental models. HB-19 inhibited colony formation in soft agar of tumor cell lines, impaired migration of endothelial cells and formation of capillary-like structures in collagen gel, and reduced blood vessel branching in the chick embryo chorioallantoic membrane. In athymic nude mice, HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in nude mice, and in some cases eliminated measurable tumors while displaying no toxicity to normal tissue. This potent antitumoral effect is attributed to the direct inhibitory action of HB-19 on both tumor and endothelial cells by blocking and down regulating surface nucleolin, but without any apparent effect on nucleolar nucleolin.
Conclusion/Significance
Our results illustrate the dual inhibitory action of HB-19 on the tumor development and the neovascularization process, thus validating the cell-surface expressed nucleolin as a strategic target for an effective cancer drug. Consequently, the HB-19 pseudopeptide provides a unique candidate to consider for innovative cancer therapy.
