The Effects of Lapatinib and Trastuzumab in a Rat Model of Endometriosis

Abstract

Trastuzumab and lapatinib are drugs belonging to tyrosine kinase inhibitors family that are used in cancer treatment to prevent cell proliferation. Trastuzumab is an inhibitor of human epidermal growth factor receptor–2 (HER2) tyrosine kinase, and lapatinib is an inhibitor of epidermal growth factor receptor (EGFR). Tyrosine kinase inhibitors have also been investigated for treatment of endometriosis. In the present study, we aimed to investigate the effects of lapatinib and trastuzumab on rat endometriosis model. Endometriosis was surgically induced by the autologous transplantation of endometrial tissue and formation of endometriosis was confirmed via secondary laparotomy in 32 rats. Initially, 4 mg/kg dose of trastuzumab was applied intraperitoneally, and two additional doses of 2 mg/kg were applied 7 days and 14 days after the initial dose. Lapatinib was administered as 100 mg/kg daily doses for 14 days. Rats were randomly divided into four groups and were subjected to lapatinib, trastuzumab, anastrozole (0.004 mg/day, p.o.) and normal saline (0.1 ml, i.p.) treatments for 14 days. Then, endometriosis foci were excised, and endometriosis scores were calculated in a semi-quantitative manner. Immunohistochemical (IHC) examinations were also performed using VEGF, CD117 and Bax antibodies. Both anastrozole and tyrosine kinase inhibitors lowered endometriosis scores. Significant decreases in ovarian follicle numbers were observed in lapatinib and anastrozole groups but not trastuzumab group. Lapatinib and trastuzumab decreased endometriotic foci through suppressing cell proliferation and promoting programmed cell death.