Combination of Fish Oil and Selenium Enhances Anticancer Efficacy and Targets Multiple Signaling Pathways in Anti-VEGF Agent Treated-TNBC Tumor-Bearing Mice
| Autor: | Guoo-Shyng W. Hsu, Ciou-Ting Fan, Yi-Chun Lin, Min-Yi Shih, Simon Hsia, Chieh-Han Chung, Pei-Chung Chen, Chih-Hung Guo, Chia-Lin Peng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell signaling
mice Pharmaceutical Science Angiogenesis Inhibitors Triple Negative Breast Neoplasms bevacizumab fish oil Article Metastasis 03 medical and health sciences Fish Oils 0302 clinical medicine Cancer stem cell Cell surface receptor antitumor mechanisms Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Drug Discovery medicine Animals Selenium Compounds selenium Pharmacology Toxicology and Pharmaceutics (miscellaneous) Transcription factor lcsh:QH301-705.5 030304 developmental biology Mice Inbred BALB C 0303 health sciences Dose-Response Relationship Drug Chemistry Kinase Avastin medicine.disease Tumor Burden lcsh:Biology (General) Apoptosis 030220 oncology & carcinogenesis Cancer research Female Signal transduction TNBC Signal Transduction |
| Zdroj: | Marine Drugs, Vol 19, Iss 193, p 193 (2021) Marine Drugs Volume 19 Issue 4 |
| ISSN: | 1660-3397 |
| Popis: | Fish oil (FO) and selenium (Se) possess antiangiogenic potential in malignant tumors. This study aimed to determine whether combination of FO and Se enhanced treatment efficacy of low-dose antiangiogenic agent Avastin (bevacizumab) in a dose-dependent manner and targeted multiple signaling pathways in triple-negative breast cancer (TNBC)-bearing mice. Randomized into five groups, mice received treatment with either physiological saline (control), Avastin alone, or Avastin in combination with low, medium, and high doses of FO/Se. The target signaling molecules for anticancer were determined either by measuring protein or mRNA expression. Avastin-treated mice receiving FO/Se showed lower tumor growth and metastasis than did mice treated with Avastin alone. Combination-treated mice exhibited lower expressions in multiple proangiogenic (growth) factors and their membrane receptors, and altered cytoplasmic signaling molecules (PI3K-PTEN-AKT-TSC-mTOR-p70S6K-4EBP1, Ras-Raf-MEK-ERK, c-Src-JAK2-STAT3-TMEPAI-Smad, LKB1-AMPK, and GSK3β/β-catenin). Dose-dependent inhibition of down-stream targets including epithelial-to-mesenchymal transition transcription factors, nuclear cyclin and cyclin-dependent kinases, cancer stem cell markers, heat shock protein (HSP-90), hypoxia-inducible factors (HIF-1α/-2α), matrix metalloprotease (MMP-9), and increased apoptosis were observed. These results suggest that combination treatment with FO and Se increases the therapeutic efficacy of Avastin against TNBC in a dose-dependent manner through multiple signaling pathways in membrane, cytoplasmic, and nucleic targets. |
| Databáze: | OpenAIRE |
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