SiRNA-HIF-1α delivered by attenuated Salmonella enhances the efficacy of Lenvatinib against hepatocellular carcinoma
Copyright © 2024 Elsevier B.V. All rights reserved..
The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1-3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
International immunopharmacology - 130(2024) vom: 30. März, Seite 111728 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Pengfei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 27.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2024.111728 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369206843 |
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| 245 | 1 | 0 | |a SiRNA-HIF-1α delivered by attenuated Salmonella enhances the efficacy of Lenvatinib against hepatocellular carcinoma |
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| 520 | |a Copyright © 2024 Elsevier B.V. All rights reserved. | ||
| 520 | |a The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1-3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HIF-1 | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a Lenvatinib | |
| 650 | 4 | |a Salmonella | |
| 650 | 4 | |a siRNA | |
| 650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
| 650 | 7 | |a lenvatinib |2 NLM | |
| 650 | 7 | |a EE083865G2 |2 NLM | |
| 650 | 7 | |a Phenylurea Compounds |2 NLM | |
| 650 | 7 | |a Quinolines |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a Vascular Endothelial Growth Factor A |2 NLM | |
| 700 | 1 | |a Wang, Yanling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xingshu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Yujing |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jinwei |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Shenning |e verfasserin |4 aut | |
| 700 | 1 | |a You, Yiqing |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yufei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Tongguo |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Xuhua |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Tiesuo |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Huijie |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Jianzhuang |e verfasserin |4 aut | |
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