Bcl-2抗凋亡癌蛋白抑制非小细胞肺癌血管生成:对光动力治疗抵抗的影响?

M. Koukourakis, A. Giatromanolaki, J. Skarlatos, L. Kosma, N. Apostolikas, K. Beroukas
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摘要

PDT细胞毒性可能通过光氧化反应发生。以这种方式,定义缺氧的机制应该参与定义光动力处理(PDT)抗性。另一方面,bcl-2抗凋亡蛋白已被证明可以延缓细胞死亡并保护细胞免受有毒氧化产物的侵害。我们检查了仅接受手术治疗的T1、2、1期患者的134例标本。使用JC70 MoAb免疫组织化学检测标本的血管分级和bcl-2癌蛋白表达。Bcl-2表达与低血管分级相关。bcl-2阳性的病例中只有3/27的血管生成高,而bcl-2不表达的病例中有34/107的血管生成高。在本研究中,我们提供了证据,证明bcl-2过表达直接抑制非小细胞肺癌血管生成,这明显导致血供和氧合减少。这一发现表明,肿瘤内血管生成的减少和永生化癌蛋白的过表达是相互关联的,并且可能在确定肿瘤对PDT具有抗性方面发挥作用。
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Bcl-2 anti-apoptotic oncoprotein suppresses angiogenesis in non-small cell lung cancer: implications in resistance to photodynamic treatment?
PDT cytotoxicity is likely to occur through photooxidative reactions. In that way mechanisms that define poor oxygenation should be involved in defining resistance to photo-dynamic treatment (PDT). On the other hand bcl-2 anti- apoptotic protein has been shown to delay cell death and protect cells from toxic oxidative products. We examined 134 specimens from T1,2-NO,1 staged patients treated with surgery alone. Specimens were immunohistochemically examined for vascular grade using the JC70 MoAb, and bcl-2 oncoprotein expression. Bcl-2 expression correlated with low vascular grade. Only 3/27 of bcl2+ case had high angiogenesis vs. 34/107 of cases without bcl-2 expression. In the present study we provide evidence that bcl-2 overexpression directly suppresses angiogenesis in non-small cell lung cancer, which obviously results in decreased blood supply and oxygenation. This finding implies that reduced intratumoral angiogenesis and immortalizing oncoprotein overexpression are linked to each other and may have a role in defining tumors resistant to PDT.
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