A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy
<p>Abstract</p> <p>Background</p> <p>The discovery of the importance of angiogenesis in tumor growth has emphasized the need to find specific vascular targets for tumor-targeted therapies. Previously, using phage display technology, we identified the peptide GX1 as havi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-09-01
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| Series: | BMC Cell Biology |
| Online Access: | http://www.biomedcentral.com/1471-2121/10/63 |
| _version_ | 1818751273249275904 |
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| author | Wang Li Du Wenqi Wan Yi Hui Xiaoli Liu Jie Wang Xin Zhang Yingqi Cao Shanshan Chen Bei Wu Kaichun Fan Daiming |
| author_facet | Wang Li Du Wenqi Wan Yi Hui Xiaoli Liu Jie Wang Xin Zhang Yingqi Cao Shanshan Chen Bei Wu Kaichun Fan Daiming |
| author_sort | Wang Li |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The discovery of the importance of angiogenesis in tumor growth has emphasized the need to find specific vascular targets for tumor-targeted therapies. Previously, using phage display technology, we identified the peptide GX1 as having the ability to target the gastric cancer vasculature. The present study investigated the bioactivities of GX1, as well as its potential ability to cooperate with recombinant mutant human tumor necrosis factor alpha (rmhTNFα), in gastric cancer therapy.</p> <p>Results</p> <p>Tetrazolium salt (MTT) assay showed that GX1 could inhibit cell proliferation of both human umbilical vein endothelial cells (HUVEC) (44%) and HUVEC with tumor endothelium characteristics, generated by culturing in tumor-conditioned medium (co-HUVEC) (62%). Flow-cytometry (FCM) and western blot assays showed that GX1 increased the rate of apoptosis from 11% to 31% (<it>p </it>< 0.01) by up-regulating caspase 3 expression level. A chorioallantoic membrane assay indicated that GX1 could suppress neovascularization <it>in vivo</it>, with the microvessel count decreasing from 21 to 11 (<it>p </it>< 0.05). When GX1 was fused to rmhTNFα, GX1-rmhTNFα selectively concentrated in the gastric cancer vasculature, as shown by enzyme-linked immunosorbent assay, immunofluorescence and emission-computed tomography. <it>In vitro </it>MTT and FCM assays showed that, compared to rmhTNFα alone, GX1-rmhTNFα was more effective at suppressing co-HUVEC proliferation (45% vs. 61%, <it>p </it>< 0.05) and inducing apoptosis (11% vs. 23%, <it>p </it>< 0.05). In a tumor formation test, GX1-rmhTNFα more effectively inhibited tumor growth than rmhTNFα (tumor volume: 271 mm<sup>3 </sup>vs. 134 mm<sup>3</sup>, <it>p </it>< 0.05), with less systemic toxicity as measured by body weight (20.57 g vs. 19.30 g, <it>p </it>< 0.05). These therapeutic effects may be mediated by selectively enhanced tumor vascular permeability, as indicated by Evan's blue assay.</p> <p>Conclusion</p> <p>GX1 had both homing activity and the ability to inhibit vascular endothelial cell proliferation <it>in vitro </it>and neovascularization <it>in vivo</it>. Furthermore, when GX1 was conjugated to rmhTNFα, the fusion protein was selectively delivered to targeted tumor sites, significantly improving the anti-tumor activity of rmhTNFα and decreasing systemic toxicity. These results demonstrate the potential of GX1 as a homing peptide in vascular targeted therapy for gastric cancer.</p> |
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| spelling | doaj.art-63d20eb947ff4a0eace0fa8db4720e512022-12-21T21:20:55ZengBMCBMC Cell Biology1471-21212009-09-011016310.1186/1471-2121-10-63A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapyWang LiDu WenqiWan YiHui XiaoliLiu JieWang XinZhang YingqiCao ShanshanChen BeiWu KaichunFan Daiming<p>Abstract</p> <p>Background</p> <p>The discovery of the importance of angiogenesis in tumor growth has emphasized the need to find specific vascular targets for tumor-targeted therapies. Previously, using phage display technology, we identified the peptide GX1 as having the ability to target the gastric cancer vasculature. The present study investigated the bioactivities of GX1, as well as its potential ability to cooperate with recombinant mutant human tumor necrosis factor alpha (rmhTNFα), in gastric cancer therapy.</p> <p>Results</p> <p>Tetrazolium salt (MTT) assay showed that GX1 could inhibit cell proliferation of both human umbilical vein endothelial cells (HUVEC) (44%) and HUVEC with tumor endothelium characteristics, generated by culturing in tumor-conditioned medium (co-HUVEC) (62%). Flow-cytometry (FCM) and western blot assays showed that GX1 increased the rate of apoptosis from 11% to 31% (<it>p </it>< 0.01) by up-regulating caspase 3 expression level. A chorioallantoic membrane assay indicated that GX1 could suppress neovascularization <it>in vivo</it>, with the microvessel count decreasing from 21 to 11 (<it>p </it>< 0.05). When GX1 was fused to rmhTNFα, GX1-rmhTNFα selectively concentrated in the gastric cancer vasculature, as shown by enzyme-linked immunosorbent assay, immunofluorescence and emission-computed tomography. <it>In vitro </it>MTT and FCM assays showed that, compared to rmhTNFα alone, GX1-rmhTNFα was more effective at suppressing co-HUVEC proliferation (45% vs. 61%, <it>p </it>< 0.05) and inducing apoptosis (11% vs. 23%, <it>p </it>< 0.05). In a tumor formation test, GX1-rmhTNFα more effectively inhibited tumor growth than rmhTNFα (tumor volume: 271 mm<sup>3 </sup>vs. 134 mm<sup>3</sup>, <it>p </it>< 0.05), with less systemic toxicity as measured by body weight (20.57 g vs. 19.30 g, <it>p </it>< 0.05). These therapeutic effects may be mediated by selectively enhanced tumor vascular permeability, as indicated by Evan's blue assay.</p> <p>Conclusion</p> <p>GX1 had both homing activity and the ability to inhibit vascular endothelial cell proliferation <it>in vitro </it>and neovascularization <it>in vivo</it>. Furthermore, when GX1 was conjugated to rmhTNFα, the fusion protein was selectively delivered to targeted tumor sites, significantly improving the anti-tumor activity of rmhTNFα and decreasing systemic toxicity. These results demonstrate the potential of GX1 as a homing peptide in vascular targeted therapy for gastric cancer.</p>http://www.biomedcentral.com/1471-2121/10/63 |
| spellingShingle | Wang Li Du Wenqi Wan Yi Hui Xiaoli Liu Jie Wang Xin Zhang Yingqi Cao Shanshan Chen Bei Wu Kaichun Fan Daiming A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy BMC Cell Biology |
| title | A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy |
| title_full | A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy |
| title_fullStr | A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy |
| title_full_unstemmed | A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy |
| title_short | A novel peptide (GX1) homing to gastric cancer vasculature inhibits angiogenesis and cooperates with TNF alpha in anti-tumor therapy |
| title_sort | novel peptide gx1 homing to gastric cancer vasculature inhibits angiogenesis and cooperates with tnf alpha in anti tumor therapy |
| url | http://www.biomedcentral.com/1471-2121/10/63 |
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