Photodynamic therapy (
PDT) is an attractive
cancer treatment modality.
Talaporfin sodium, a second-generation
photosensitizer, results in lower systemic toxicity and relatively better selective
tumor destruction than first-generation
photosensitizers. However, the mechanism through which
PDT induces vascular shutdown is unclear. In this study, the in vitro effects of
talaporfin sodium-based
PDT on human umbilical vein endothelial cells (HUVECs) were determined through cell viability and endothelial tube formation assays, and evaluation of the
tubulin and
F-actin dynamics and
myosin light chain (MLC) phosphorylation. Additionally, the effects on
tumor blood flow and
tumor vessel destruction were assessed in vivo. In the HUVECs,
talaporfin sodium-based
PDT induced endothelial tube destruction and microtubule depolymerization, triggering the formation of
F-actin stress fibers and a significant increase in MLC phosphorylation. However, pretreatment with the Rho-associated
protein kinase (ROCK) inhibitor,
Y27632, completely prevented
PDT-induced stress fiber formation and MLC phosphorylation. The in vivo analysis and pathological examination revealed that the
PDT had significantly decreased the
tumor blood flow and the active area of the
tumor vessel. We concluded that
talaporfin sodium-based
PDT induces the shutdown of existing
tumor vessels via the RhoA/ROCK pathway by activating the Rho-
GTP pathway and decreasing the
tumor blood flow.