Vascular disrupting effects of combretastatin A4 phosphate on murine endometriotic lesions
This study demonstrates for the first time a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for the therapy of endometriosis.
Dilu Feng, M.D., Michael D. Menger, M.D., Matthias W. Laschke, M.D., Ph.D.
Volume 100, Issue 5, Pages 1459-1467.e1, November 2013
To study the effect of combretastatin A4 phosphate (CA4P) on the vascularization of endometriotic lesions.
Intravital microscopic, histologic, and immunohistochemical study.
Murine endometriotic lesions were induced by syngeneic transplantation of endometrium into dorsal skinfold chambers. After 6 days, the mice received an intraperitoneal injection of 80 mg/kg CA4P or vehicle.
Main Outcome Measure(s):
Vascularization of the lesions and the surrounding tissue was analyzed by intravital fluorescence microscopy over 8 days. Lesion morphology, vessel maturation, viability, and proliferation of endometrial glands and stroma were assessed by histology and immunohistochemistry.
All lesions were initially well vascularized, containing immature and mature microvessels. Injection of CA4P induced a selective vessel collapse in the lesions without affecting the surrounding microvasculature. This resulted in a decreased functional capillary density and blood perfusion of CA4P-treated lesions after 2 hours when compared with controls. However, the vascularization of the lesions progressively normalized, and their numbers of proliferating and apoptotic cells did not differ from those of controls.
This study demonstrates a selective vascular disrupting effect of CA4P on endometriotic lesions, indicating that vascular disrupting agents may be suitable for endometriosis therapy.