State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xian 710032, China.
Cancer Lett. 2011 Oct 28;309(2):220-7. doi: 10.1016/j.canlet.2011.06.008. Epub 2011 Jun 24.
Notch signaling plays an important role in vascular development and tumor angiogenesis. It has been shown that disruption of Dll4-triggered Notch signal activation effectively inhibits tumor growth, but this treatment also results in the formation of vascular neoplasms. In this study, we investigate the effects of over-expressing Notch ligand Dll1 in B16 melanoma cells on tumor cell proliferation and tumor growth in vitro and in vivo. Our results showed that over-expression of Dll1 could activate Notch signaling in tumor cells, and promote tumor cell proliferation in vitro. In contrast, growth of Dll1-over-expressing tumors in vivo was reduced, due to abnormal tumor vessel formation. Impaired tumor vasculature enhanced hypoxia and necrosis in tumor tissues, leading to retarded tumor growth. These results suggest that activation of Notch signaling may serve as an anti-angiogenesis strategy in the treatment of malignant tumors.
Notch 信号通路在血管发育和肿瘤血管生成中发挥着重要作用。已有研究表明，阻断 Dll4 触发的 Notch 信号激活可有效抑制肿瘤生长，但该治疗方法也会导致血管肿瘤的形成。在这项研究中，我们研究了在 B16 黑色素瘤细胞中过表达 Notch 配体 Dll1 对肿瘤细胞增殖和体内外肿瘤生长的影响。结果表明，Dll1 的过表达可激活肿瘤细胞中的 Notch 信号通路，并促进肿瘤细胞在体外的增殖。相比之下，由于肿瘤血管形成异常，Dll1 过表达肿瘤的生长在体内受到抑制。受损的肿瘤血管使肿瘤组织中的缺氧和坏死加重，导致肿瘤生长缓慢。这些结果表明，激活 Notch 信号通路可能成为治疗恶性肿瘤的抗血管生成策略。
