Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo

Abstract Osteosarcoma is the most common primary bone cancer in children and adolescents. In spite of aggressive treatment, osteosarcoma has a high mortality rate with minimal improvements in survival over past few decades. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb P...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Junli Chang, Yimian Li, Xianyang Wang, Shaopu Hu, Hongshen Wang, Qi Shi, Yongjun Wang, Yanping Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e1992a1a4d1943fc933377c51b9a9e30
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e1992a1a4d1943fc933377c51b9a9e30
record_format	dspace
spelling	oai:doaj.org-article:e1992a1a4d1943fc933377c51b9a9e302021-12-02T11:40:57ZPolyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo10.1038/s41598-017-07194-92045-2322https://doaj.org/article/e1992a1a4d1943fc933377c51b9a9e302017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07194-9https://doaj.org/toc/2045-2322Abstract Osteosarcoma is the most common primary bone cancer in children and adolescents. In spite of aggressive treatment, osteosarcoma has a high mortality rate with minimal improvements in survival over past few decades. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb Paris polyphylla Smith, has been shown to have anti-tumor properties. However, its mechanism as an anti-osteosarcoma agent has not been well elucidated. In this study, we found that PPI suppressed osteosarcoma cell viability, arrested cell cycle in G2/M phase, induced apoptosis and inhibited invasion and migration of osteosarcoma cells. Moreover, PPI significantly suppressed intratibial primary tumor growth in xenograft orthotopic mouse model without any obvious side effects. These therapeutic efficacies were associated with inactivation of Wnt/β-catenin pathway, as PPI treatment decreased the amount of p-GSK-3β, leading to down-regulated levels of active β-catenin. PPI induced inhibition of osteosarcoma cell viability was abolished upon addition of GSK-3β specific inhibitor, CHIR99021, while PPI induced inhibition of osteosarcoma cell viability and migration were potentiated by β-catenin silencing. These findings suggested that, in vitro and in vivo, PPI treatment inhibited osteosarcoma, at least in part, via the inactivation of Wnt/β-catenin pathway. Thus, PPI could serve a novel therapeutic option for osteosarcoma patients.Junli ChangYimian LiXianyang WangShaopu HuHongshen WangQi ShiYongjun WangYanping YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Junli Chang Yimian Li Xianyang Wang Shaopu Hu Hongshen Wang Qi Shi Yongjun Wang Yanping Yang Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo
description	Abstract Osteosarcoma is the most common primary bone cancer in children and adolescents. In spite of aggressive treatment, osteosarcoma has a high mortality rate with minimal improvements in survival over past few decades. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb Paris polyphylla Smith, has been shown to have anti-tumor properties. However, its mechanism as an anti-osteosarcoma agent has not been well elucidated. In this study, we found that PPI suppressed osteosarcoma cell viability, arrested cell cycle in G2/M phase, induced apoptosis and inhibited invasion and migration of osteosarcoma cells. Moreover, PPI significantly suppressed intratibial primary tumor growth in xenograft orthotopic mouse model without any obvious side effects. These therapeutic efficacies were associated with inactivation of Wnt/β-catenin pathway, as PPI treatment decreased the amount of p-GSK-3β, leading to down-regulated levels of active β-catenin. PPI induced inhibition of osteosarcoma cell viability was abolished upon addition of GSK-3β specific inhibitor, CHIR99021, while PPI induced inhibition of osteosarcoma cell viability and migration were potentiated by β-catenin silencing. These findings suggested that, in vitro and in vivo, PPI treatment inhibited osteosarcoma, at least in part, via the inactivation of Wnt/β-catenin pathway. Thus, PPI could serve a novel therapeutic option for osteosarcoma patients.
format	article
author	Junli Chang Yimian Li Xianyang Wang Shaopu Hu Hongshen Wang Qi Shi Yongjun Wang Yanping Yang
author_facet	Junli Chang Yimian Li Xianyang Wang Shaopu Hu Hongshen Wang Qi Shi Yongjun Wang Yanping Yang
author_sort	Junli Chang
title	Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo
title_short	Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo
title_full	Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo
title_fullStr	Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo
title_full_unstemmed	Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo
title_sort	polyphyllin i suppresses human osteosarcoma growth by inactivation of wnt/β-catenin pathway in vitro and in vivo
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e1992a1a4d1943fc933377c51b9a9e30
work_keys_str_mv	AT junlichang polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo AT yimianli polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo AT xianyangwang polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo AT shaopuhu polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo AT hongshenwang polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo AT qishi polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo AT yongjunwang polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo AT yanpingyang polyphyllinisuppresseshumanosteosarcomagrowthbyinactivationofwntbcateninpathwayinvitroandinvivo
_version_	1718395552582860800

Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo

Ejemplares similares