美國韋克福雷斯特大學26日發(fā)布消息說,,該校醫(yī)學院的研究人員日前通過動物實驗發(fā)現(xiàn),一種名為血管緊縮素(1-7)的小肽可以通過抑制血管形成的方式阻止癌細胞生長,。
研究人員首先在兩組實驗鼠體內(nèi)培育了肺癌細胞,,其中一組注射血管緊縮素(1-7)進行治療,另一組注射生理鹽水作為對照,。6周后,,研究人員發(fā)現(xiàn),接受血管緊縮素(1-7)治療的實驗鼠體內(nèi)腫瘤明顯縮小,,大小只有對照組實驗鼠體內(nèi)腫瘤的40%,。此外,前者體內(nèi)腫瘤中血管的數(shù)量也明顯少于后者,。
研究人員通過雞胚實驗進一步研究了血管緊縮素(1-7)對血管形成的影響,。他們發(fā)現(xiàn),注射生理鹽水的雞胚血管正常生長,,而注射血管緊縮素(1-7)的雞胚血管數(shù)量下降了一半以上,。
研究人員指出,血管是腫瘤獲取營養(yǎng)從而不斷增殖的重要渠道,,抑制腫瘤內(nèi)血管的形成對治療癌癥具有重要意義,。他們的實驗表明,,血管緊縮素(1-7)可能不僅對肺癌有效,或許還可以抑制乳腺癌,、結(jié)腸癌等癌癥的發(fā)展,。這項研究成果已刊登在美國《分子癌癥治療學》雜志上。(生物谷Bioon.com)
生物谷推薦原始出處:
Mol Cancer Ther June 1, 2009 8, 1676 doi: 10.1158/1535-7163.MCT-09-0161
Angiotensin-(1-7) inhibits tumor angiogenesis in human lung cancer xenografts with a reduction in vascular endothelial growth factor
David R. Soto-Pantoja1,2, Jyotsana Menon1,3, Patricia E. Gallagher1,3 and E. Ann Tallant1,2,3
1Hypertension and Vascular Research Center, 2Molecular Genetics and Genomics Program, and 3Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina
Angiotensin-(1-7) [Ang-(1-7)] is an endogenous seven-amino acid peptide hormone with antiproliferative properties. Our previous studies showed that Ang-(1-7) inhibits the growth of human lung cancer cells in vitro and reduces the size of human lung tumor xenografts in vivo. In the current study, s.c. injection of Ang-(1-7) not only caused a significant reduction in human A549 lung tumor growth but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. A decrease in human endothelial cell tubule formation in Matrigel was observed following a 16 h incubation with Ang-(1-7), with a maximal reduction at a 10 nmol/L concentration. Ang-(1-7) had similar antiangiogenic effects in the chick chorioallantoic membrane, causing a >50% decrease in neovascularization. The Ang-(1-7)-induced reduction in both endothelial cell tubule formation and vessel formation in the chick was completely blocked by the specific Ang-(1-7) receptor antagonist [d-proline7]-Ang-(1-7), suggesting that these biological actions are mediated by an AT(1-7) receptor. Ang-(1-7) significantly reduced vascular endothelial growth factor-A protein and mRNA in tumors from mice treated with the heptapeptide compared with saline controls as well as in the parent A549 human lung cancer cells in culture. These results suggest that Ang-(1-7) may attenuate tumor angiogenesis by reducing vascular endothelial growth factor-A, a primary proangiogenic protein. Taken together, this study shows that Ang-(1-7) exhibits significant antiangiogenic activity and may be a novel therapeutic agent for lung cancer treatment targeting a specific AT(1-7) receptor.