Blockage of gonadrotropin-releasing hormone (GnRH) receptor (GnRHR) leads to a decrease in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release from the pituitary, and subsequently testosterone production from testes is suppressed. Degarelix is a GnRHR antagonist used in patients with prostate cancer (PCa) who need androgen deprivation therapy (ADT). In vitro, cell viability of different prostate cells was decreased after 24, 48, or 72h of treatment with 10 μM degarelix. Furthermore, degarelix treatment induced a significant increase on caspase 3/7 activation compared to control in normal, hyperplasia, and cancer cells indicating that cells were undergoing apoptosis using the caspase cascade[3]. In vivo, at single subcutaneous injections of 0.3 to 10 μg/kg in rats, degarelix produced a dose-dependent suppression of the pituitary-gonadal axis as revealed by the decrease in plasma LH and testosterone levels[4].
Degarelix/地加瑞克 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Splenocytes
1 µM
48 h
To evaluate the effect of Degarelix on splenocyte proliferation, results showed no significant effect on proliferation.
J Am Heart Assoc. 2016 Feb 23;5(2):e002800
Bone marrow-derived macrophages
1 µM
24 h
To evaluate the effect of Degarelix on cytokine secretion from LPS-stimulated macrophages, results showed no significant effect on IL-6, MCP-1, and TNF-α secretion.
J Am Heart Assoc. 2016 Feb 23;5(2):e002800
Degarelix/地加瑞克 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Apoe-deficient mice
Apoe-deficient mouse model
Subcutaneous injection
0.5 mg
Every 4 weeks for 18 weeks
To evaluate the effect of Degarelix on atherosclerosis in Apoe-deficient mice, results showed that Degarelix reduced plasma testosterone levels, increased total cholesterol levels, but did not significantly affect the progression of atherosclerosis.
J Am Heart Assoc. 2016 Feb 23;5(2):e002800
Male Sprague-Dawley rats
Orchidectomised or chemically castrated model
Subcutaneous injection
2 mg/kg
Two injections, 6 weeks apart, for 10 weeks
To evaluate the effects of Degarelix on the androgen-deficient osteoporosis rat model, showing that Degarelix significantly reduced serum testosterone levels and induced adverse changes in bone structure and metabolism.
Nutrients. 2018 Jun 21;10(7):799
FVB mice
Myc-CaP prostate tumor model
Subcutaneous injection
25 mg/kg
Every 28 days
To evaluate the antitumor efficacy of Degarelix in combination with targeted radionuclide therapy (TRT) in prostate tumor models. Results showed that the ADT→TRT sequence significantly delayed tumor growth and improved overall survival.
J Immunother Cancer. 2024 Apr 24;12(4):e008760
Mice
LNCaP-AR or VCaP human prostate cancer xenograft models
Subcutaneous or intraperitoneal injection
0.5 mg/mouse
Single dose
To evaluate the inhibitory effect of degarelix in combination with VTP on tumor growth in prostate cancer xenograft models. Results showed that the combination of degarelix and VTP significantly inhibited tumor growth, superior to degarelix or VTP alone.
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