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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2021
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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) |
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Ghrelin Cisplatin Ovarian cancer Cell cycle S phase arrest CDK1 Gynecology and obstetrics RG1-991 |
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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 |
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