Wyld L, Reed M W, Brown N J
The Department of Surgical and Anaesthetic Sciences, Sheffield University, Royal Hallamshire Hospital, UK.
Br J Cancer. 1998 May;77(10):1621-7. doi: 10.1038/bjc.1998.265.
Photodynamic therapy (PDT) is a cancer treatment based on the interaction of light and a photosensitizing chemical. The photosensitizer protoporphyrin IX (PpIX) is generated via the haem biosynthetic pathway after administration of aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic and acidotic relative to normal tissue, which may influence PpIX generation and compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA at various oxygen tensions and H+ ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15, 0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1) respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was enhanced at lower pH values. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT.
光动力疗法（PDT）是一种基于光与光敏化学物质相互作用的癌症治疗方法。在给予氨基乙酰丙酸（ALA）后，通过血红素生物合成途径生成光敏剂原卟啉IX（PpIX）。相对于正常组织，肿瘤的细胞微环境是缺氧和酸性的，这可能会影响PpIX的生成并损害PDT的疗效。本研究使用膀胱癌细胞，在不同的氧张力和H+离子浓度下与ALA孵育，并评估对PpIX生成和PDT敏感性的影响。与21%（160 mmHg）氧浓度相比，在0%、2.5%（19 mmHg）和5%（38 mmHg）氧浓度下PpIX的产生减少（分别为0.15、0.28和0.398 ng μg-1蛋白质，而在21%氧浓度下为0.68 ng μg-1；P < 0.05）。缺氧消除了对PDT的反应，这是由于PpIX合成减少和PDT毒性降低所致。与pH 7.4和5.5（分别为0.41和0.55 ng μg-1）相比，在pH 7.0和6.5（0.75和0.66 ng μg-1）时PpIX的产生更多。在较低的pH值下，PDT细胞毒性增强。这些结果表明，由于内在PpIX合成减少，缺氧可能会抑制ALA诱导的PDT。酸中毒可能会略微增强ALA诱导的PDT的疗效。
