Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells

Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of...

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Autores principales: Yun Leng, Can Zhao, Guoliang Yan, Shuangyue Xu, Yinggui Yang, Ting Gong, Xin Li, Chenglin Li
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Lenguaje:EN
Publicado: BMC 2021
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Acceso en línea:https://doaj.org/article/3c17689f14f34f60b7bf4f4733970817
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spelling oai:doaj.org-article:3c17689f14f34f60b7bf4f47339708172021-11-21T12:32:12ZGhrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells10.1186/s13048-021-00907-91757-2215https://doaj.org/article/3c17689f14f34f60b7bf4f47339708172021-11-01T00:00:00Zhttps://doi.org/10.1186/s13048-021-00907-9https://doaj.org/toc/1757-2215Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism. Methods The anti-tumor effects of ghrelin and cisplatin were evaluated with human ovarian cancer cells HO-8910 PM in vitro or in vivo. Cell apoptosis and cell cycle were analyzed via flow cytometry assay. The signaling pathway and the expression of cell cycle protein were analyzed with Western Blot. Results Our results showed that treatment with ghrelin specifically inhibited cell proliferation of HO-8910 PM and sensitized these cells to cisplatin via S phase cell cycle arrest, and enhanced the inhibitory effect of cisplatin on tumor growth of HO-8910 PM derived xenografts in vivo. Treatment with ghrelin inhibited the expression of p-Erk1/2 and p-p38, which was opposite the effect of cisplatin. However, under the treatment of ghrelin, cisplatin treatment exhibited a stronger effect on inhibiting P21 expression, upregulating p-CDK1 and cyclin B1 expression, and blocking cell cycle progression. Mechanistically, ghrelin promoted S phase cell cycle arrest and upregulated p-CDK1 and cyclin B1 expression induced by cisplatin via inhibition of p38. Conclusion This study revealed a specifically inhibitory effect of ghrelin on platinum-resistance via suppressing p-P38 and subsequently promoting p-CDK1 mediated cell cycle arrest in HO-8910 PM.Yun LengCan ZhaoGuoliang YanShuangyue XuYinggui YangTing GongXin LiChenglin LiBMCarticleGhrelinCisplatinOvarian cancerCell cycleS phase arrestCDK1Gynecology and obstetricsRG1-991ENJournal of Ovarian Research, Vol 14, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Ghrelin
Cisplatin
Ovarian cancer
Cell cycle
S phase arrest
CDK1
Gynecology and obstetrics
RG1-991
spellingShingle Ghrelin
Cisplatin
Ovarian cancer
Cell cycle
S phase arrest
CDK1
Gynecology and obstetrics
RG1-991
Yun Leng
Can Zhao
Guoliang Yan
Shuangyue Xu
Yinggui Yang
Ting Gong
Xin Li
Chenglin Li
Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells
description Abstract Background Resistance to platinum-based chemotherapy is one of the crucial problems in ovarian cancer treatment. Ghrelin, a widely distributed peptide hormone, participates in a series of cancer progression. The aim of this study is to determine whether ghrelin influences the sensitivity of ovarian cancer to cisplatin, and to demonstrate the underlying mechanism. Methods The anti-tumor effects of ghrelin and cisplatin were evaluated with human ovarian cancer cells HO-8910 PM in vitro or in vivo. Cell apoptosis and cell cycle were analyzed via flow cytometry assay. The signaling pathway and the expression of cell cycle protein were analyzed with Western Blot. Results Our results showed that treatment with ghrelin specifically inhibited cell proliferation of HO-8910 PM and sensitized these cells to cisplatin via S phase cell cycle arrest, and enhanced the inhibitory effect of cisplatin on tumor growth of HO-8910 PM derived xenografts in vivo. Treatment with ghrelin inhibited the expression of p-Erk1/2 and p-p38, which was opposite the effect of cisplatin. However, under the treatment of ghrelin, cisplatin treatment exhibited a stronger effect on inhibiting P21 expression, upregulating p-CDK1 and cyclin B1 expression, and blocking cell cycle progression. Mechanistically, ghrelin promoted S phase cell cycle arrest and upregulated p-CDK1 and cyclin B1 expression induced by cisplatin via inhibition of p38. Conclusion This study revealed a specifically inhibitory effect of ghrelin on platinum-resistance via suppressing p-P38 and subsequently promoting p-CDK1 mediated cell cycle arrest in HO-8910 PM.
format article
author Yun Leng
Can Zhao
Guoliang Yan
Shuangyue Xu
Yinggui Yang
Ting Gong
Xin Li
Chenglin Li
author_facet Yun Leng
Can Zhao
Guoliang Yan
Shuangyue Xu
Yinggui Yang
Ting Gong
Xin Li
Chenglin Li
author_sort Yun Leng
title Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells
title_short Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells
title_full Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells
title_fullStr Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells
title_full_unstemmed Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells
title_sort ghrelin enhances cisplatin sensitivity in ho-8910 pm human ovarian cancer cells
publisher BMC
publishDate 2021
url https://doaj.org/article/3c17689f14f34f60b7bf4f4733970817
work_keys_str_mv AT yunleng ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
AT canzhao ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
AT guoliangyan ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
AT shuangyuexu ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
AT yingguiyang ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
AT tinggong ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
AT xinli ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
AT chenglinli ghrelinenhancescisplatinsensitivityinho8910pmhumanovariancancercells
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