Effects of a lytic peptide conjugated to β hCG on ovarian cancer: Studies in vitro and in vivo

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Objective. The aim of this study was to determine the in vitro and in vivo effects of the lytic peptide, hecate, alone and conjugated to a 15-amino-acid fragment of the β-chain of hCG (hecate-β hCG) on the ovarian carcinoma cell line NIH: OVCAR-3 and determine the expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors in cell cultures and tumor tissues. Methods. For in vitro studies, hecate or hecate-β hCG was added to cultures of ovarian cancer cells in the presence or absence of estradiol or follicle stimulating hormone. The cytotoxicity of lytic peptides was measured by trypan blue exclusion and lactate dehydrogenase release. For in vivo studies, OVCAR-3 xenografts were established in female athymic nude mice which were then treated once per week for 3 weeks with hecate or hecate-β hCG via the lateral tail vein. An immunohistochemical method was used to analyze the expression of LH/hCG receptor in tumor and culture cells. Results. In in vitro studies, both hecate-β hCG and hecate destroyed ovarian cancer cells (NIH: OVCAR-3) in a dose-dependent manner. Removal of steroids from the culture medium reduced the sensitivity of the OVCAR-3 cell line to the hecate-β hCG in a reversible manner. In in vivo studies, the average tumor volume and tumor burden in lytic peptide treated animals were reduced. In the groups of animals treated by hecate, hecate-β hCG, and estradiol + hecate-β hCG, tumor volumes after treatment expressed as a percentage of increase (197.4 ± 21.72, 199.0 ± 18.57, and 193.8 ± 22.94%, respectively) were reduced, compared to control (263.0 ± 21.72%) animals (P < 0.05). Immunocytochemical studies revealed the expression of LH/hCG receptor protein in the OVCAR-3 cells and tumor tissues. Conclusion. Hecate-β hCG is a putative candidate for treating ovarian cancer. © 2002 Elsevier Science (USA).

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Gynecologic Oncology

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