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A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy

BACKGROUND: Stemness of CD133(+)EPCAM(+) hepatocellular carcinoma cells ensures cancer resistance to apoptosis,which is a challenge to current liver cancer treatments. In this study, we evaluated the tumorcidal activity of a novel nanoparticle of nitidine chloride (TPGS-FA/NC, TPGS-FA: folic acid mo...

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Detalles Bibliográficos
Autores principales: Li, Danni, Zhang, Qiying, Zhou, Yuzhu, Zhu, Hua, Li, Tong, Du, Fangkai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277916/
https://www.ncbi.nlm.nih.gov/pubmed/35820920
http://dx.doi.org/10.1186/s40360-022-00589-z
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author Li, Danni
Zhang, Qiying
Zhou, Yuzhu
Zhu, Hua
Li, Tong
Du, Fangkai
author_facet Li, Danni
Zhang, Qiying
Zhou, Yuzhu
Zhu, Hua
Li, Tong
Du, Fangkai
author_sort Li, Danni
collection PubMed
description BACKGROUND: Stemness of CD133(+)EPCAM(+) hepatocellular carcinoma cells ensures cancer resistance to apoptosis,which is a challenge to current liver cancer treatments. In this study, we evaluated the tumorcidal activity of a novel nanoparticle of nitidine chloride (TPGS-FA/NC, TPGS-FA: folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate, NC: nitidine chloride), against human hepatocellular carcinoma (HCC) cell line Huh7 growth in vitro and in vivo. METHODS: Huh7 cells were treated with TPGS-FA/NC. Cell proliferation was assessed using MTT and colony assays. The expression of cell markers and signaling proteins was detected using western blot analyses. A sphere culture technique was used to enrich cancer stem cells (CSC) in Huh7 cells. TPGS-FA/NC (7.5, 15, 30, 60, 120 μg/mL) dose-dependently inhibited the proliferation of HCC cells, which associated with a reduction in AQP3 and STAT3 expression. Importantly,TPGS-FA/NC (10, 20, and 40 μg/mL) significantly reduced the EpCAM(+)/CD133(+)cell numbers, suppressed the sphere formation. The in vivo antitumor efficacy of TPGS-FA/NC was proved in Huh7 cell xenograft model in BALB/c nude mice, which were administered TPGS-FA/NC(4 mg· kg − 1· d − 1, ig) for 2 weeks. RESULTS: TPGS-FA/NC dose-dependently suppressed the AQP3/STAT3/CD133 axis in Huh7 cells. In Huh7 xenograft bearing nude mice, TPGS-FA/NC administration markedly inhibited Huh7 xenograft tumor growth . CONCLUSIONS: TPGS-FA/NC inhibit HCC tumor growth through multiple mechanisms, and it may be a promising candidate drug for the clinical therapy of hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40360-022-00589-z.
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spelling pubmed-92779162022-07-14 A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy Li, Danni Zhang, Qiying Zhou, Yuzhu Zhu, Hua Li, Tong Du, Fangkai BMC Pharmacol Toxicol Research BACKGROUND: Stemness of CD133(+)EPCAM(+) hepatocellular carcinoma cells ensures cancer resistance to apoptosis,which is a challenge to current liver cancer treatments. In this study, we evaluated the tumorcidal activity of a novel nanoparticle of nitidine chloride (TPGS-FA/NC, TPGS-FA: folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate, NC: nitidine chloride), against human hepatocellular carcinoma (HCC) cell line Huh7 growth in vitro and in vivo. METHODS: Huh7 cells were treated with TPGS-FA/NC. Cell proliferation was assessed using MTT and colony assays. The expression of cell markers and signaling proteins was detected using western blot analyses. A sphere culture technique was used to enrich cancer stem cells (CSC) in Huh7 cells. TPGS-FA/NC (7.5, 15, 30, 60, 120 μg/mL) dose-dependently inhibited the proliferation of HCC cells, which associated with a reduction in AQP3 and STAT3 expression. Importantly,TPGS-FA/NC (10, 20, and 40 μg/mL) significantly reduced the EpCAM(+)/CD133(+)cell numbers, suppressed the sphere formation. The in vivo antitumor efficacy of TPGS-FA/NC was proved in Huh7 cell xenograft model in BALB/c nude mice, which were administered TPGS-FA/NC(4 mg· kg − 1· d − 1, ig) for 2 weeks. RESULTS: TPGS-FA/NC dose-dependently suppressed the AQP3/STAT3/CD133 axis in Huh7 cells. In Huh7 xenograft bearing nude mice, TPGS-FA/NC administration markedly inhibited Huh7 xenograft tumor growth . CONCLUSIONS: TPGS-FA/NC inhibit HCC tumor growth through multiple mechanisms, and it may be a promising candidate drug for the clinical therapy of hepatocellular carcinoma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40360-022-00589-z. BioMed Central 2022-07-12 /pmc/articles/PMC9277916/ /pubmed/35820920 http://dx.doi.org/10.1186/s40360-022-00589-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Li, Danni
Zhang, Qiying
Zhou, Yuzhu
Zhu, Hua
Li, Tong
Du, Fangkai
A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy
title A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy
title_full A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy
title_fullStr A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy
title_full_unstemmed A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy
title_short A novel nitidine chloride nanoparticle overcomes the stemness of CD133(+)EPCAM(+) Huh7 hepatocellular carcinoma cells for liver cancer therapy
title_sort novel nitidine chloride nanoparticle overcomes the stemness of cd133(+)epcam(+) huh7 hepatocellular carcinoma cells for liver cancer therapy
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277916/
https://www.ncbi.nlm.nih.gov/pubmed/35820920
http://dx.doi.org/10.1186/s40360-022-00589-z
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