The role of nitric oxide in the treatment of tumours with aminolaevulinic acid-induced photodynamic therapy

作者：Reeves K J^*; Reed M W R; Brown N J

来源：Journal of Photochemistry and Photobiology B: Biology , 2010, 101(3): 224-232.

DOI：10.1016/j.jphotobiol.2010.07.007

• Aminolaevulinic acid
• Photodynamic therapy
• Nitric oxide
• Nitric oxide synthase inhibitors
• In vivo microscopy
• Tumours

Photodynamic therapy (PDT) is a local cancer treatment which Induces cell death by the interaction of light with a photosensitizing drug Previous studies indicate that nitric oxide (NO) plays a role in Photofrin-PDT but this has not been investigated in aminolaevulinic acid (ALA)-PDT The current study determines whether inhibition of nitric oxide synthase (NOS) activity modulates treatment responses to ALA-PDT in tumours displaying differential levels of NO
Murine tumours with low (EMT6) or high (RIF-1) NO levels were Implanted into the cremaster muscle of BALB/c or C3H/HeN mice respectively Animals were prepared for in vivo microscopy 7-14 days later Mice received oral ALA (200 mg/kg) 4 h before PDT L-NAME L-NNA or 1400 W (10 mg/kg) were administered via the jugular vein 5 min before PDT
NOS inhibition (L-NAME or L-NNA) combined with ALA-PDT in RIF-1 tumours demonstrated enhanced damage to both the tumour and normal microvasculature with increased macromolecular leak and reduction in vessel diameter whereas ALA-PDT alone had no effect In contrast EMT6 tumours responded to ALA-PDT alone but sensitivity was not enhanced in the presence of NOS inhibition 1400 W combined with ALA-PDT induced similar microvascular effects to L-NAME in both tumours but were less pronounced <b

• 出版日期2010-12-2