Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H

Background Celastrus orbiculatus ethyl acetate extract (COE) has shown a strong anti-gastric cancer effect, but the understanding of its mechanism is still lacking. The results of previous studies indicated that COE may be able to inhibit the stemness of gastric cancer stem cells (GCSCs) by regulati...

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Autores principales:	Yao-dong Zhu MD, He Ba Bachelor of Medicine, Jie Chen Bachelor of Medicine, Mei Zhang MD, Ping Li MD
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ab44492fd06a491b9a463fa45ad66c92
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spelling	oai:doaj.org-article:ab44492fd06a491b9a463fa45ad66c922021-11-21T02:03:53Z Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H1534-73541552-695X10.1177/15347354211058168https://doaj.org/article/ab44492fd06a491b9a463fa45ad66c922021-11-01T00:00:00Zhttps://doi.org/10.1177/15347354211058168https://doaj.org/toc/1534-7354https://doaj.org/toc/1552-695XBackground Celastrus orbiculatus ethyl acetate extract (COE) has shown a strong anti-gastric cancer effect, but the understanding of its mechanism is still lacking. The results of previous studies indicated that COE may be able to inhibit the stemness of gastric cancer stem cells (GCSCs) by regulating PDCD4 and EIF3H expression. Aims To explore if COE could inhibit the stemness of GCSCs by regulating PDCD4 and EIF3H expression in vitro and in vivo. Procedure The GCSCs model was established by stem cell-conditioned culture. Spheroid formation and flow cytometry assays were used to detect the effect of COE on the spheroid formation ability of GCSCs and the percentage of CD44 + /CD24 + and ALDH + cell subpopulations. Western blot analysis was applied to measure the expression of GCSCs biomarkers (Nanog, Oct-4, and SOX-2), PDCD4, and EIF3H in GCSCs treated with COE; and RT-PCR was performed to investigate the effect of COE on PDCD4 mRNA expression in GCSCs. An in vivo tumorigenicity experiment was also conducted to evaluate the effect of COE on tumor-initiating ability of GCSCs in vivo; and the expression of PDCD4 and EIF3H in xenograft tissues was examined by immunohistochemistry (IHC) staining. Results After culture in stem cell-conditioned medium, SGC7901 cells manifested significantly enhanced spheroid formation ability, upregulated Nanog, Oct-4, and SOX-2 expression and increased percentages of CD44 + /CD24 + and ALDH + cell subpopulations, indicating successful establishment of the GCSCs model. COE treatment significantly inhibited the spheroid formation ability of GCSCs and reduced the percentage of CD44 + /CD24 + and ALDH + cell subpopulations. The western blot analysis showed a significant decrease of Nanog, Oct-4, SOX-2, and EIF3H expression and an increase of PDCD4 expression in GCSCs after COE treatment in a concentration-dependent manner. COE treatment also significantly upregulated the mRNA expression of PDCD4 in GCSCs. In addition, COE displayed a strong inhibitory effect on the tumor-initiating ability of GCSCs in vivo and upregulated PDCD4 and downregulated EIF3H expression in xenograft tissues. Conclusion COE may be able to inhibit GC growth by suppressing the stemness of GCSCs via regulating PDCD4 and EIF3H expression.Yao-dong Zhu MDHe Ba Bachelor of MedicineJie Chen Bachelor of MedicineMei Zhang MDPing Li MDSAGE PublishingarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENIntegrative Cancer Therapies, Vol 20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yao-dong Zhu MD He Ba Bachelor of Medicine Jie Chen Bachelor of Medicine Mei Zhang MD Ping Li MD Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H
description	Background Celastrus orbiculatus ethyl acetate extract (COE) has shown a strong anti-gastric cancer effect, but the understanding of its mechanism is still lacking. The results of previous studies indicated that COE may be able to inhibit the stemness of gastric cancer stem cells (GCSCs) by regulating PDCD4 and EIF3H expression. Aims To explore if COE could inhibit the stemness of GCSCs by regulating PDCD4 and EIF3H expression in vitro and in vivo. Procedure The GCSCs model was established by stem cell-conditioned culture. Spheroid formation and flow cytometry assays were used to detect the effect of COE on the spheroid formation ability of GCSCs and the percentage of CD44 + /CD24 + and ALDH + cell subpopulations. Western blot analysis was applied to measure the expression of GCSCs biomarkers (Nanog, Oct-4, and SOX-2), PDCD4, and EIF3H in GCSCs treated with COE; and RT-PCR was performed to investigate the effect of COE on PDCD4 mRNA expression in GCSCs. An in vivo tumorigenicity experiment was also conducted to evaluate the effect of COE on tumor-initiating ability of GCSCs in vivo; and the expression of PDCD4 and EIF3H in xenograft tissues was examined by immunohistochemistry (IHC) staining. Results After culture in stem cell-conditioned medium, SGC7901 cells manifested significantly enhanced spheroid formation ability, upregulated Nanog, Oct-4, and SOX-2 expression and increased percentages of CD44 + /CD24 + and ALDH + cell subpopulations, indicating successful establishment of the GCSCs model. COE treatment significantly inhibited the spheroid formation ability of GCSCs and reduced the percentage of CD44 + /CD24 + and ALDH + cell subpopulations. The western blot analysis showed a significant decrease of Nanog, Oct-4, SOX-2, and EIF3H expression and an increase of PDCD4 expression in GCSCs after COE treatment in a concentration-dependent manner. COE treatment also significantly upregulated the mRNA expression of PDCD4 in GCSCs. In addition, COE displayed a strong inhibitory effect on the tumor-initiating ability of GCSCs in vivo and upregulated PDCD4 and downregulated EIF3H expression in xenograft tissues. Conclusion COE may be able to inhibit GC growth by suppressing the stemness of GCSCs via regulating PDCD4 and EIF3H expression.
format	article
author	Yao-dong Zhu MD He Ba Bachelor of Medicine Jie Chen Bachelor of Medicine Mei Zhang MD Ping Li MD
author_facet	Yao-dong Zhu MD He Ba Bachelor of Medicine Jie Chen Bachelor of Medicine Mei Zhang MD Ping Li MD
author_sort	Yao-dong Zhu MD
title	Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H
title_short	Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H
title_full	Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H
title_fullStr	Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H
title_full_unstemmed	Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H
title_sort	extract reduces stemness of gastric cancer stem cells by targeting pdcd4 and eif3h
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/ab44492fd06a491b9a463fa45ad66c92
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Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H

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