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Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p

Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and t...

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Autores principales: Gu, Xian, Zhu, Ling-yu, Xu, Zhen-ye, Shen, Ke-ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093395/
https://www.ncbi.nlm.nih.gov/pubmed/33959499
http://dx.doi.org/10.3389/fonc.2021.630921
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author Gu, Xian
Zhu, Ling-yu
Xu, Zhen-ye
Shen, Ke-ping
author_facet Gu, Xian
Zhu, Ling-yu
Xu, Zhen-ye
Shen, Ke-ping
author_sort Gu, Xian
collection PubMed
description Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs.
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spelling pubmed-80933952021-05-05 Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p Gu, Xian Zhu, Ling-yu Xu, Zhen-ye Shen, Ke-ping Front Oncol Oncology Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs. Frontiers Media S.A. 2021-04-20 /pmc/articles/PMC8093395/ /pubmed/33959499 http://dx.doi.org/10.3389/fonc.2021.630921 Text en Copyright © 2021 Gu, Zhu, Xu and Shen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gu, Xian
Zhu, Ling-yu
Xu, Zhen-ye
Shen, Ke-ping
Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
title Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
title_full Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
title_fullStr Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
title_full_unstemmed Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
title_short Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p
title_sort astragaloside iv and saponins of rhizoma polygonati cure cyclophosphamide-induced myelosuppression in lung adenocarcinoma via down-regulating mir-142-3p
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093395/
https://www.ncbi.nlm.nih.gov/pubmed/33959499
http://dx.doi.org/10.3389/fonc.2021.630921
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