CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma
Abstract This study aims to discover the therapeutic effect of chemokine (CXC motif) receptor 4 (CXCR4) antagonist AMD3100 combined with transcatheter arterial chemoembolization (TACE) in a rat model with hepatocellular carcinoma (HCC). An orthotopic model of HCC was established and treated with T...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12540 |
| _version_ | 1818487457524482048 |
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| author | Hong‐Wei Lei Bi‐Run Huang Jie Cai Cheng‐Ming Li Chun‐Bo Shang Zhi‐Yang Liao Zheng‐Dong Wan |
| author_facet | Hong‐Wei Lei Bi‐Run Huang Jie Cai Cheng‐Ming Li Chun‐Bo Shang Zhi‐Yang Liao Zheng‐Dong Wan |
| author_sort | Hong‐Wei Lei |
| collection | DOAJ |
| description | Abstract This study aims to discover the therapeutic effect of chemokine (CXC motif) receptor 4 (CXCR4) antagonist AMD3100 combined with transcatheter arterial chemoembolization (TACE) in a rat model with hepatocellular carcinoma (HCC). An orthotopic model of HCC was established and treated with TACE (doxorubicin‐lipiodol emulsion) with or without AMD3100. The tumor volume was measured by magnetic resonance imaging (MRI). Histopathological changes were detected by hematoxylin–eosin (HE) staining. HCC cell apoptosis was assessed by terminal deoxyribonucleotidyl transferase (TdT)‐mediated biotin‐16‐dUTP nick‐end labeling (TUNEL) staining. Immunohistochemistry was used to detect the expression of CD34, hypoxia‐inducible factor 1α (HIF‐1α), vascular endothelial growth factor (VEGF), and Ki67. Gene and protein expressions were quantified by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and western blotting, respectively. Both TACE and AMD3100 reduced the tumor volume in orthotopic rat model of HCC with the decreased CXCR4 expression in tumor tissues, and the combination had better effect. However, TACE increased the microvessel density (MVD) in HCC tissues of rats, while AMD3100 treatment reduced MVD in HCC tissues. AMD3100 reduced the TACE induced MVD in HCC tissues with the reduction of HIF‐1α and VEGF expression. Either AMD3100 or TACE could promote HCC cell apoptosis accompanying by decreased cell proliferation, and their combined use had better therapeutic effects. CXCR4 antagonist AMD3100 enhance therapeutic efficacy of TACE in rats with HCC via promoting the HCC cell apoptosis, reducing cell proliferation, and inhibiting MVD, thus reducing tumor volume. |
| first_indexed | 2024-12-10T16:37:54Z |
| format | Article |
| id | doaj.art-8c787be47eb644b09d83dc448809e1d2 |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-12-10T16:37:54Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-8c787be47eb644b09d83dc448809e1d22022-12-22T01:41:19ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502022-08-0138878178910.1002/kjm2.12540CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinomaHong‐Wei Lei0Bi‐Run Huang1Jie Cai2Cheng‐Ming Li3Chun‐Bo Shang4Zhi‐Yang Liao5Zheng‐Dong Wan6Department of Interventional Vascular Surgery The First Affiliated Hospital of Yangtze University Jingzhou ChinaDepartment of Interventional Vascular Surgery The First Affiliated Hospital of Yangtze University Jingzhou ChinaDepartment of Interventional Vascular Surgery The First Affiliated Hospital of Yangtze University Jingzhou ChinaDepartment of Interventional Vascular Surgery The First Affiliated Hospital of Yangtze University Jingzhou ChinaDepartment of Interventional Vascular Surgery The First Affiliated Hospital of Yangtze University Jingzhou ChinaDepartment of Interventional Vascular Surgery The First Affiliated Hospital of Yangtze University Jingzhou ChinaDepartment of Interventional Vascular Surgery The First Affiliated Hospital of Yangtze University Jingzhou ChinaAbstract This study aims to discover the therapeutic effect of chemokine (CXC motif) receptor 4 (CXCR4) antagonist AMD3100 combined with transcatheter arterial chemoembolization (TACE) in a rat model with hepatocellular carcinoma (HCC). An orthotopic model of HCC was established and treated with TACE (doxorubicin‐lipiodol emulsion) with or without AMD3100. The tumor volume was measured by magnetic resonance imaging (MRI). Histopathological changes were detected by hematoxylin–eosin (HE) staining. HCC cell apoptosis was assessed by terminal deoxyribonucleotidyl transferase (TdT)‐mediated biotin‐16‐dUTP nick‐end labeling (TUNEL) staining. Immunohistochemistry was used to detect the expression of CD34, hypoxia‐inducible factor 1α (HIF‐1α), vascular endothelial growth factor (VEGF), and Ki67. Gene and protein expressions were quantified by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and western blotting, respectively. Both TACE and AMD3100 reduced the tumor volume in orthotopic rat model of HCC with the decreased CXCR4 expression in tumor tissues, and the combination had better effect. However, TACE increased the microvessel density (MVD) in HCC tissues of rats, while AMD3100 treatment reduced MVD in HCC tissues. AMD3100 reduced the TACE induced MVD in HCC tissues with the reduction of HIF‐1α and VEGF expression. Either AMD3100 or TACE could promote HCC cell apoptosis accompanying by decreased cell proliferation, and their combined use had better therapeutic effects. CXCR4 antagonist AMD3100 enhance therapeutic efficacy of TACE in rats with HCC via promoting the HCC cell apoptosis, reducing cell proliferation, and inhibiting MVD, thus reducing tumor volume.https://doi.org/10.1002/kjm2.12540AMD3100CXCR4hepatocellular carcinomatranscatheter arterial chemoembolization |
| spellingShingle | Hong‐Wei Lei Bi‐Run Huang Jie Cai Cheng‐Ming Li Chun‐Bo Shang Zhi‐Yang Liao Zheng‐Dong Wan CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma Kaohsiung Journal of Medical Sciences AMD3100 CXCR4 hepatocellular carcinoma transcatheter arterial chemoembolization |
| title | CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma |
| title_full | CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma |
| title_fullStr | CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma |
| title_full_unstemmed | CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma |
| title_short | CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma |
| title_sort | cxcr4 antagonist amd3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma |
| topic | AMD3100 CXCR4 hepatocellular carcinoma transcatheter arterial chemoembolization |
| url | https://doi.org/10.1002/kjm2.12540 |
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