Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo
Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study ai...
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Elsevier
2023-05-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023034990 |
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author | Nayereh Bahamin Mahmoud Rafieian-Kopaei Shahin Ahmadian Iraj Karimi Amir Hossein Doustimotlagh Gholamreza Mobini Elham Bijad Mahshid Shafiezadeh |
author_facet | Nayereh Bahamin Mahmoud Rafieian-Kopaei Shahin Ahmadian Iraj Karimi Amir Hossein Doustimotlagh Gholamreza Mobini Elham Bijad Mahshid Shafiezadeh |
author_sort | Nayereh Bahamin |
collection | DOAJ |
description | Breast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of β-catenin (β-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of β-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit β-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment. |
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institution | Directory Open Access Journal |
issn | 2405-8440 |
language | English |
last_indexed | 2024-03-13T08:23:46Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
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spelling | doaj.art-6ab32517633a44d1b31dbdbace8eb2da2023-05-31T04:47:08ZengElsevierHeliyon2405-84402023-05-0195e16292Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivoNayereh Bahamin0Mahmoud Rafieian-Kopaei1Shahin Ahmadian2Iraj Karimi3Amir Hossein Doustimotlagh4Gholamreza Mobini5Elham Bijad6Mahshid Shafiezadeh7Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran; Corresponding author.Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran; Corresponding author.Pathobiology Department, Veterinary Faculty, Shahrekord University, Shahrekord, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran; Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, IranCancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, IranMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, IranDepartment of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, IranBreast cancer is a challenging disease and leading cause of cancer death in women. There is no effective agent for metastatic breast cancer after surgery and chemotherapy. Alhagi maurorum (A.m) has been reported to exhibit an anticancer effect on various types of cancer cells in vitro. This study aimed to examine the suppressive effect of A.m alone and combined with docetaxel (DTX) on the breast cancer growth in mice models and the possible underlying mechanisms. In the present study, the mice were inoculated subcutaneously with the injections of 4T1 cells. Then, A.m, DTX, and their combination were administered intraperitoneally. The expressions of β-catenin (β-cat), FZD7, MMP2, HIF1-α, and VEGF A (vascular endothelial growth factor A) were investigated using RT-PCR method. Also, plasma alkaline phosphatase (ALP), alanine aminotransferase (GPT or ALT), aspartate transaminase (GOT or AST), serum creatinine, and urea were examined, and histological analyses of the tissues were conducted. The results demonstrated that A.m (500 mg/kg) combined with DTX significantly decreased the expression of β-cat, MMP2, and FZD7 as compared with the negative control group and monotherapies. Also, the mRNA levels of HIF1-α and VEGF A were suppressed significantly by DTX + A.m (500 mg/kg). Tumor weights and sizes were significantly lower and tumor inhibition rate was significantly higher in the DTX + A.m group. The A.m 500 mg/kg + DTX also suppressed the serum GPT level in tumor-bearing mice and decreased the serum urea level. Taken together, our findings suggest that DTX combined with A.m at an optimal dose of 500 mg/kg as the optimal dose can inhibit β-cat, FZD7, MMP2, and breast cancer growth via interrupting HIF-1α/VEGF signaling and might be used as a promising antiangiogenic agent for breast cancer treatment.http://www.sciencedirect.com/science/article/pii/S2405844023034990Breast cancerA. maurorumDocetaxelAngiogenesisSynergy |
spellingShingle | Nayereh Bahamin Mahmoud Rafieian-Kopaei Shahin Ahmadian Iraj Karimi Amir Hossein Doustimotlagh Gholamreza Mobini Elham Bijad Mahshid Shafiezadeh Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo Heliyon Breast cancer A. maurorum Docetaxel Angiogenesis Synergy |
title | Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo |
title_full | Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo |
title_fullStr | Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo |
title_full_unstemmed | Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo |
title_short | Combined treatment with Alhagi maurorum and docetaxel inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vivo |
title_sort | combined treatment with alhagi maurorum and docetaxel inhibits breast cancer progression via targeting hif 1α vegf mediated tumor angiogenesis in vivo |
topic | Breast cancer A. maurorum Docetaxel Angiogenesis Synergy |
url | http://www.sciencedirect.com/science/article/pii/S2405844023034990 |
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