Low-dose glucocorticoids suppresses ovarian tumor growth and metastasis in an immunocompetent syngeneic mouse model

Autor: Lu-Hai Wang, Shu-Pin Sun, Kai-Ti Lin, Jui-I Wu
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Transcription
Genetic
Physiology
Cancer Treatment
lcsh:Medicine
Pathology and Laboratory Medicine
Dexamethasone
Metastasis
Ovarian tumor
0302 clinical medicine
Cell Movement
Immune Physiology
Basic Cancer Research
Medicine and Health Sciences
Neoplasm Metastasis
lcsh:Science
Ovarian Neoplasms
Innate Immune System
Multidisciplinary
Animal Models
Debulking
Ovarian Cancer
Cancer Cell Migration
Up-Regulation
Gene Expression Regulation
Neoplastic
Cell Motility
Experimental Organism Systems
Oncology
030220 oncology & carcinogenesis
Cytokines
Female
Inflammation Mediators
Immunocompetence
hormones
hormone substitutes
and hormone antagonists
Research Article
Signal Transduction
endocrine system
Immunology
Down-Regulation
Mouse Models
Cell Migration
Research and Analysis Methods
Immune Suppression
Models
Biological
Proinflammatory cytokine
03 medical and health sciences
Model Organisms
Signs and Symptoms
Diagnostic Medicine
Cell Line
Tumor
medicine
Animals
Metastasis suppressor
Neoplasm Invasiveness
Animal Models of Disease
Glucocorticoids
Cell Proliferation
Tumor microenvironment
Dose-Response Relationship
Drug
business.industry
Macrophages
Myeloid-Derived Suppressor Cells
lcsh:R
Cancers and Neoplasms
Biology and Life Sciences
Cell Biology
Molecular Development
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
MicroRNAs
030104 developmental biology
rap GTP-Binding Proteins
Immune System
Cancer research
Myeloid-derived Suppressor Cell
Animal Studies
lcsh:Q
Ovarian cancer
business
Gynecological Tumors
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 6, p e0178937 (2017)
ISSN: 1932-6203
Popis: Ovarian cancer has the highest mortality rate among gynecologic malignancies. Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently with a poor prognosis. We previously reported a novel role of glucocorticoids (GCs) in metastatic ovarian cancer by upregulating microRNA-708. In this study, we used an immunocompetent syngeneic mouse model and further evaluated the effect and optimal dosages of GCs in treating metastatic ovarian cancer. The treatment of C57BL/6-derived ovarian cancer ID-8 cells with a synthetic GC, dexamethasone (DEX), induced the expression of microRNA-708, leading to decreased cell migration and invasion through targeting Rap1B. Administration of DEX at a low dose, as low as 5 μg/kg body weight, inhibited the primary tumor size and abdominal metastasis in mice bearing ID-8 cell-derived ovarian tumors. In the treated primary tumors, microRNA-708 was upregulated, whereas some proinflammatory cytokines, namely interleukin (IL)-1β and IL-18, were downregulated. The number of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment were reduced. Overall, our study shows that low-dose GCs can suppress ovarian cancer progression and metastasis likely through not only the upregulation of the metastasis suppressor microRNA-708, but also the modulation of TAMs and MDSCs in the tumor microenvironment.
Databáze: OpenAIRE
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