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Liposomal prednisolone inhibits tumor growth in a spontaneous mouse mammary carcinoma model
- Source :
- Journal of Controlled Release, 243, 243. Elsevier, Journal of controlled release, 243, 243-249. Elsevier
- Publication Year :
- 2016
-
Abstract
- Cancers are abundantly infiltrated by inflammatory cells that are modulated by tumor cells to secrete mediators fostering tumor cell survival and proliferation. Therefore, agents that interfere with inflammatory signaling molecules or specific immune cell populations have been investigated as anticancer drugs. Corticosteroids are highly potent anti-inflammatory drugs, whose activity is intensified when targeted by nanocarrier systems. Liposome-targeted corticosteroids have been shown to inhibit tumor growth in different syngeneic murine tumor models as well as human xenograft mouse models, which is attributed to a switch in the tumor microenvironment from a pro-inflammatory to an anti-inflammatory state. Despite the recognized value of implantation tumor models in preclinical research, the “acute” inflammation induced by inoculation of tumor cells together with the exponential tumor growth in a relatively short period of time does not resemble slow progressive human disease that develops in situ. Therefore, in this study, the antitumor effect of liposomal corticosteroids was investigated in a clinically more relevant setting of transgenic mice developing spontaneous breast carcinomas. Here we show that liposomal prednisolone phosphate inhibits the growth of spontaneous breast carcinoma. Interestingly, the liposomal prednisolone was significantly more active than free drug. At 72 h after injection of the liposomal formulation, 3 μg prednisolone per gram of tumor tissue was recovered whereas no drug could be recovered after injection of the free agent. This indicates that, despite etiological and morphological differences between implanted and spontaneous tumor models, EPR-mediated accumulation of drug occurs to similar extent in this spontaneous mammary carcinoma model as in the syngeneic tumor models. Finally, we analyzed miRNA profiles in the MMTV/neu model and showed that the top 10 of miRNAs in the MMTV/neu tumor consisted of miRNAs with a known involvement in breast carcinoma proliferation and metastasis. The only exception was the appearance of miR-146b, a known inflammation-regulating miRNA species, after liposomal prednisolone treatment.
- Subjects :
- 0301 basic medicine
Genetically modified mouse
Cell signaling
Pathology
medicine.medical_specialty
Time Factors
METIS-320735
Antineoplastic Agents, Hormonal
Prednisolone
Pharmaceutical Science
Mice, Transgenic
Inflammation
Metastasis
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Journal Article
Animals
Humans
Secretion
Spontaneous breast cancer
Glucocorticoids
Tumor microenvironment
business.industry
Mammary Neoplasms, Experimental
IR-103526
medicine.disease
Xenograft Model Antitumor Assays
MicroRNAs
030104 developmental biology
030220 oncology & carcinogenesis
Liposomes
miRNAs
Cancer research
Female
medicine.symptom
business
Breast carcinoma
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 01683659
- Database :
- OpenAIRE
- Journal :
- Journal of Controlled Release, 243, 243. Elsevier, Journal of controlled release, 243, 243-249. Elsevier
- Accession number :
- edsair.doi.dedup.....fc1270a8dcd096a63efae1c5c518c241