Cucurbitacin B modulates M2 macrophage differentiation and attenuates osteosarcoma progression via PI3K/AKT pathway

Fuente: Wiley Open Access
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Autores principales: Hong Wu, Tianjun Ma, Mei He, Wenkai Xie, Xueyan Wang, Liuping Lu, Hui Wang, Ying Cui
Formato: Artículo Open Access
Publicado: Wiley 2024
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author Hong Wu
Tianjun Ma
Mei He
Wenkai Xie
Xueyan Wang
Liuping Lu
Hui Wang
Ying Cui
author_facet Hong Wu
Tianjun Ma
Mei He
Wenkai Xie
Xueyan Wang
Liuping Lu
Hui Wang
Ying Cui
Hong Wu
Tianjun Ma
Mei He
Wenkai Xie
Xueyan Wang
Liuping Lu
Hui Wang
Ying Cui
collection Wiley Open Access
contents Cucurbitacin B modulates M2 macrophage differentiation and attenuates osteosarcoma progression via PI3K/AKT pathway Hong Wu Tianjun Ma Mei He Wenkai Xie Xueyan Wang Liuping Lu Hui Wang Ying Cui Phytotherapy Research AbstractOsteosarcoma is a common malignant bone tumour characterised by an aggressive metastatic potential. The tumour microenvironment, particularly the M2‐polarised macrophages, is crucial for tumour progression. Cucurbitacin B (CuB), a triterpenoid derivative, is recognised for its anti‐inflammatory and antitumour properties. This study investigates CuB and its effect on M2 macrophage differentiation and osteosarcoma progression, aiming to contribute to new treatment strategies. In vitro, THP‐1 monocytes were stimulated with PMA, IL‐13 and IL‐4 to induce differentiation into M2 macrophages. Additionally, the influence of CuB on the proliferation, migration and invasion of osteosarcoma cells in the context of M2 macrophages was scrutinised. Crucial signalling pathways, especially the PI3K/AKT pathway, affected by CuB were identified and validated. In vivo, the osteosarcoma model was employed to gauge the effects of CuB on tumour weight, lung metastasis, angiogenesis, cell proliferation and M2 macrophage markers. The results showed that CuB inhibited M2 macrophage differentiation, leading to reduced proliferation, migration and invasion of osteosarcoma cells. CuB manifested an inhibitory effect on the PI3K/AKT pathway during the differentiation of M2 macrophages. In mouse models, CuB markedly reduced the tumour weight and the number of lung metastases. It also reduced the expression of angiogenesis and cell proliferation markers in tumour tissues, decreased the quantity of M2 macrophages and their associated markers and pathway proteins. In conclusion, CuB impedes osteosarcoma progression by inhibiting M2 macrophage differentiation via the PI3K/AKT pathway, presenting the potential for therapeutic advancements in osteosarcoma treatment. 10.1002/ptr.8146 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/ptr.8146
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institution Wiley Open Access
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publishDate 2024
publisher Wiley
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spellingShingle Cucurbitacin B modulates M2 macrophage differentiation and attenuates osteosarcoma progression via PI3K/AKT pathway
Hong Wu
Tianjun Ma
Mei He
Wenkai Xie
Xueyan Wang
Liuping Lu
Hui Wang
Ying Cui
Phytotherapy Research
Cucurbitacin B modulates M2 macrophage differentiation and attenuates osteosarcoma progression via PI3K/AKT pathway Hong Wu Tianjun Ma Mei He Wenkai Xie Xueyan Wang Liuping Lu Hui Wang Ying Cui Phytotherapy Research AbstractOsteosarcoma is a common malignant bone tumour characterised by an aggressive metastatic potential. The tumour microenvironment, particularly the M2‐polarised macrophages, is crucial for tumour progression. Cucurbitacin B (CuB), a triterpenoid derivative, is recognised for its anti‐inflammatory and antitumour properties. This study investigates CuB and its effect on M2 macrophage differentiation and osteosarcoma progression, aiming to contribute to new treatment strategies. In vitro, THP‐1 monocytes were stimulated with PMA, IL‐13 and IL‐4 to induce differentiation into M2 macrophages. Additionally, the influence of CuB on the proliferation, migration and invasion of osteosarcoma cells in the context of M2 macrophages was scrutinised. Crucial signalling pathways, especially the PI3K/AKT pathway, affected by CuB were identified and validated. In vivo, the osteosarcoma model was employed to gauge the effects of CuB on tumour weight, lung metastasis, angiogenesis, cell proliferation and M2 macrophage markers. The results showed that CuB inhibited M2 macrophage differentiation, leading to reduced proliferation, migration and invasion of osteosarcoma cells. CuB manifested an inhibitory effect on the PI3K/AKT pathway during the differentiation of M2 macrophages. In mouse models, CuB markedly reduced the tumour weight and the number of lung metastases. It also reduced the expression of angiogenesis and cell proliferation markers in tumour tissues, decreased the quantity of M2 macrophages and their associated markers and pathway proteins. In conclusion, CuB impedes osteosarcoma progression by inhibiting M2 macrophage differentiation via the PI3K/AKT pathway, presenting the potential for therapeutic advancements in osteosarcoma treatment. 10.1002/ptr.8146 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Cucurbitacin B modulates M2 macrophage differentiation and attenuates osteosarcoma progression via PI3K/AKT pathway
topic Phytotherapy Research
url https://onlinelibrary.wiley.com/doi/10.1002/ptr.8146