Effects of a lytic peptide conjugated to beta HCG on ovarian cancer: studies in vitro and in vivo.
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 beta-chain of hCG (hecate-beta 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-beta 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-beta 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-beta 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-beta 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-beta hCG, and estradiol + hecate-beta 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.


CONCLUSIONS
Hecate-beta hCG is a putative candidate for treating ovarian cancer.
Gawronska
Barbara
B
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 30803, USA. gawronB@pbrc.edu
Leuschner
Carola
C
Enright
Frederick M
FM
Hansel
William
W
D000818:Animals; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008555:Melitten / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011974:Receptors, LH / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D018997:Chorionic Gonadotropin, beta Subunit, Human; D011974:Receptors, LH; C098827:hecate 1; D008555:Melitten