Activity of Pertuzumab Administration on a Rodent Model of Endometriosis

Endometriosis is an invasive and chronic pathology, prone to metastasis, characterized by the presence of endometrial stroma and glands outside the uterus. Pertuzumab is a monoclonal antibody usually employed as anticancer drug. It is mainly used in patients with HER2 positive, unresectable, metastatic or locally relapsed breast and uterine cancer who have not previously been treated with anti‐HER2 therapy or chemotherapy for metastatic disease.Endometriosis was induced in female animals by intraperitoneal injection with the equivalent of tissue from one uterus (1:1 donor/recipient ratio) along the midventral line. The development of the lesions was allowed in the intraperitoneal region for seven days. Recipient animals were then randomly assigned to the following treatment group: vehicle and Pertuzumab (15 mg/Kg). Animals received a series of subcutaneous injections on days two and six after tissue injection and were euthanized on day fourteen. The peritoneal cavities of the recipient animals were inspected and the lesions were carefully removed and measured. The endometrial‐like tissue was confirmed by histology, Masson trichrome and Toluidine Blue were employed to assess fibrosis and mast cells recruitment respectively. In the treated group, the cysts area was significantly smaller, the fibrosis score improved and mast cells number decreased. Pertuzumab administration decreased angiogenesis (VEGF), serum hypoxia‐inducible factor‐1alpha (HIF‐1alpha), intercellular adhesion molecule (ICAM), matrix metalloproteinases (MMP9) expression and lymphocyte accumulation. Pertuzumab also reduced peroxynitrite formation, PARP activation, IkBa phosphorylation and NFkB traslocation in the nucleus. Our results suggested that Pertuzumab may be of useful to inhibit development of endometriotic lesions.