Research Article

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

Volume: 43 Number: 4 December 27, 2022
EN

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.

Keywords

References

  1. [1] Giudice L.C., Endometriosis, Clinical practice, N. Engl. J. Med., 362 (25) (2010) 2389-98.
  2. [2] Harel Z., Dysmenorrhea in adolescents and young adults: an update on pharmacological treatments and management strategies, Expert Opin Pharmacother., 13 (15) (2012) 2157-70.
  3. [3] Simoens S., Dunselman G., Dirksen C., Hummelshoj L., Bokor A., Brandes I, et al., The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres, Hum. Reprod., 27 (5) (2012) 1292-9.
  4. [4] Jiang Q.Y., Wu R.J., Growth mechanisms of endometriotic cells in implanted places: a review, Gynecol Endocrinol., 28 (7) (2012) 562-7.
  5. [5] Nisolle M., Donnez J., Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities, Fertil Steril., 68 (4) (1997) 585-96.
  6. [6] Möller B., Rasmussen C., Lindblom B., Olovsson M., Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle, Mol Hum Reprod., 7 (1) (2001) 65-72.
  7. [7] Huang J.C., Papasakelariou C., Dawood M.Y., Epidermal growth factor and basic fibroblast growth factor in peritoneal fluid of women with endometriosis, Fertil Steril., 65 (5) (1996) 931-4.
  8. [8] Abe W., Nasu K., Tsuno A., Kawano Y., Narahara H., Phosphatidylinositol-3 kinase-Akt-mammalian target of rapamycin signaling pathway mediates contractility of human endometriotic stromal cells: A promising new target for the treatment of endometriosis-associated fibrosis, Gynecol Minim Invasive Ther., 3 (4) (2014) 115-8.

Details

Primary Language

English

Subjects

Structural Biology

Journal Section

Research Article

Publication Date

December 27, 2022

Submission Date

August 30, 2022

Acceptance Date

November 24, 2022

Published in Issue

Year 2022 Volume: 43 Number: 4

APA
Yıldız, Ç., Özsoy, Z., Kacan, T., & Özer, H. (2022). The Effects of Lapatinib and Trastuzumab in a Rat Model of Endometriosis. Cumhuriyet Science Journal, 43(4), 556-563. https://doi.org/10.17776/csj.1168698

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