Harmey Judith H, Bouchier-Hayes David
Department of Surgery, Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Bioessays. 2002 Mar;24(3):280-3. doi: 10.1002/bies.10043.
Angiogenesis is central to both the growth and metastasis of solid tumours. Anti-angiogenic strategies result in blood vessel regression accompanied by tumour cell apoptosis. Radiotherapy and many chemotherapeutic agents kill tumours by inducing apoptotic cell death. We propose that, in addition to its role as an angiogenic factor, vascular endothelial growth factor (VEGF) can act as a survival factor for tumour cells protecting them from apoptosis. Thus anti-angiogenics, in particular those directed against VEGF, have multiple anti-tumour effects. We suggest that anti-VEGF strategies prevent vessel growth and block a tumour cell survival factor, VEGF, rendering tumour cells more sensitive to chemotherapy and radiotherapy. In addition, as chemotherapy and radiotherapy have been shown to increase VEGF expression, anti-VEGF strategies may overcome therapy- induced tumour cell resistance.
血管生成对于实体瘤的生长和转移都至关重要。抗血管生成策略会导致血管退缩并伴有肿瘤细胞凋亡。放疗和许多化疗药物通过诱导凋亡性细胞死亡来杀死肿瘤。我们提出,血管内皮生长因子(VEGF)除了作为血管生成因子发挥作用外,还可作为肿瘤细胞的存活因子,保护它们免于凋亡。因此,抗血管生成药物,尤其是那些针对VEGF的药物,具有多种抗肿瘤作用。我们认为,抗VEGF策略可阻止血管生长并阻断肿瘤细胞存活因子VEGF,使肿瘤细胞对化疗和放疗更敏感。此外,由于已证明化疗和放疗会增加VEGF表达,抗VEGF策略可能克服治疗诱导的肿瘤细胞耐药性。