Controlled release low dose medroxyprogesterone acetate (MPA) inhibits the development of mammary tumors induced by dimethyl-benz(a) anthracene in the rat
Abstract
Medroxyprogesterone acetate (MPA) is well recognized to have beneficial effects for the treatment of advanced breast cancer which are comparable to those achieved with other forms of endocrine therapy. Using mammary tumors induced in the rat by dimethylbenz(a)anthracene (DMBA) as a model, we have studied the possibility that low dose MPA could prevent the development of these tumors. Single subcutaneous injection of Depo-Provera (crystalline suspension of MPA) or MPA encapsulated in biodegradable microspheres of 50:50 poly[DL-lactide-co-glycolide] was given 7 days before oral DMBA. While 63% of intact animals developed palpable mammary tumors within 85 days after DMBA administration, tumor incidence decreased to 28% and 23% in animals who had received 30 mg and 100 mg of Depo-Provera, respectively. The same amounts of MPA delivered in microspheres caused a further decrease in tumor incidence to respective values of 7% and 6%. Average tumor area, on the other hand, decreased from 4.89 cm2 in intact rats to about 0.75 (0.57-0.88) cm2 and approximately 0.20 (0.14-0.22) cm2 in the Depo-Provera and microsphere-treated groups, respectively. Using the 50:50 formulation of poly[DL-lactide-co-glycolide] designed to release MPA at a constant rate for a 4-month period, the serum MPA concentration at 3 months was measured at 4.99 +/- 0.43 ng/ml. Such data suggest that administration of a low dose controlled-release formulation of MPA in 50:50 poly[DL-lactide-co-glycolide] microspheres could well be an efficient and well tolerated approach for the prevention of breast cancer in women.
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Controlled release of low-dose MPA exerts a potent inhibitory effect on development and growth of DMBA-induced mammary carcinoma in the rat.
“in vivo studies have demonstrated that controlled release of low-dose MPA, a compound having androgenic activity, also exerts a potent inhibitory effect on the development and growth of DMBA-induced mammary carcinoma in the rat (243, 244).”
From Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone (2003) · cites this paper as [244]
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Labrie, F., Luu-The, V., Labrie, C., Bélanger, A., Simard, J., Lin, S.-X., & Pelletier, G. (2003) · Endocrine Reviews · doi:10.1210/er.2001-0031 · Cited by 544 · see citing works
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Self-citation
- Authors
- Labrie, F., Li, S., B�langer, A., C�t�, J., M�rand, Y., & Lepage, M.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Venue
- Breast Cancer Research and Treatment
- Published
- 1993
- Volume
- 26
- Issue
- 3
- Pages
- 253-265
- ISSN
- 0167-6806 (ISSN-L)
- 1573-7217
- OpenAlex
- W2072095147
- Cited by
- 18
- References
- 58
- Citations by year
- 2023: 1
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Breast Cancer Research and Treatment (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- medroxyprogesterone acetate, controlled release, breast cancer prevention, dimethylbenz[a]anthracene, mammary tumors, endocrine therapy, low-dose progestin, tumor incidence, tumor size, serum drug concentration
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Chemistry, Pharmaceutical, Delayed-Action Preparations, Dose-Response Relationship, Drug, Female, Injections, Subcutaneous, Mammary Neoplasms, Experimental, Microspheres, Polyglycolic Acid, Polymers, 9,10-Dimethyl-1,2-benzanthracene, Rats, Sprague-Dawley, Medroxyprogesterone Acetate, Lactic Acid, Rats
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