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Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers

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机构: [1]1 Department of Respiratory and Critical Care Medicine, Xinqiao Hospital, The Army Medical University, Chongqing 400037, China [2]Department of Pathology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, Sichuan Province 646000, China [3]The First Clinical Institute, Zunyi Medical University, Zunyi, Guizhou Province 563003, China [4]Department of Human Anatomy, School of Basic Medical Sciences, Southwest Medical University, No. 1, Section 1, Xianglin Road, Matan Long District, Luzhou, Sichuan Province 646000, China
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关键词: Alantolactone STAT3 MAPK pathway BRAF Melanoma Drug resistance

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Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.© 2024. The Author(s).

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大类 | 2 区 医学
小类 | 3 区 肿瘤学
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第一作者机构: [1]1 Department of Respiratory and Critical Care Medicine, Xinqiao Hospital, The Army Medical University, Chongqing 400037, China
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