The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: The role of OGFr, BCL2, and immune response
| Autor: | Fleur F. Abd Elmonem, mohammed Labib Salem, Mohamed Nabih Abdel Rahman, Sabah H. El-Ghaiesh, Alshimaa Aboalsoud |
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| Rok vydání: | 2020 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
0301 basic medicine Immunology Down-Regulation Apoptosis Pharmacology OGFr Mice 03 medical and health sciences 0302 clinical medicine Immune system Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Splenocyte Carcinoma Animals Humans Immunologic Factors Immunology and Allergy Medicine Carcinoma Ehrlich Tumor business.industry Myeloid-Derived Suppressor Cells Cancer Off-Label Use medicine.disease Naltrexone Gene Expression Regulation Neoplastic 030104 developmental biology Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Receptors Opioid Cancer cell Myeloid-derived Suppressor Cell Female Fluorouracil Low-dose naltrexone Drug Screening Assays Antitumor business |
| Zdroj: | International Immunopharmacology. 78:106068 |
| ISSN: | 1567-5769 |
| Popis: | Aims Cancer is a major worldwide health problem. Cancer cells express opioid growth factor (OGF) which controls their growth. Naltrexone in low dose (LDN) blocks opioid receptors intermittently and controls the replication of cancer cells. The aim of this study was to investigate the effect of LDN and its chemotherapeutic additive effect on the growth of solid Ehrlich carcinoma in mice with focus on the OGFr and immune responses. Main methods Sixty female Swiss albino mice were assigned into 5 groups (n: 12 mice each): (i): normal control, (ii): Solid Ehrlich carcinoma (SEC), (iii): SEC treated with LDN, (iv): SEC treated with 5-fluorouracil (5-FU), (v): SEC treated with LDN + 5-FU. All drugs were started when the tumor became palpable on 9th day. At the end of the study animals were sacrificed, blood and tissue samples were collected. Tumor weight and volume were measured. Splenocytes and myeloid derived suppressor cells (MDSC) were counted. Tumor expression of opioid growth factor receptors (OGFr), serum level of IFN-γ, tumor histopathology (H&E) and immunohistochemistry staining of p21, p53, Bcl2 were assessed. Key findings All drug-treated groups showed reduction in tumor weight and volume, significant increase of splenocyte with tendency to reduce MDSC cell counts. LDN led to significant increase in OGFr both in solo and in combination with 5FU. Serum IFN-γ is significantly increased by LDN but decreased by 5-FU. Also, LDN and 5FU increased immunehistochemical staining of p21 while decreased immunostaining of Bcl2. In animals treated with a combination of LDN and 5FU a maximal downregulation of the antiapoptotic mediator BCL2 was observed. Significance The current study suggested that LDN may play a role in inhibiting cancer cell growth and highlights the possibility of promising combination with cancer chemotherapeutics, which guarantee further clinical studies for approval. |
| Databáze: | OpenAIRE |
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