Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells.
Ghrelin enhances cisplatin sensitivity in HO-8910 PM human ovarian cancer cells.
复制标题
Ghrelin 增强 HO-8910-PM 人卵巢癌细胞对顺铂的敏感性
DOI：
10.1186/s13048-021-00907-9
复制
发表时间：
2021-11-17
影响因子：
4
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Leng Y;Zhao C;Yan G;Xu S;Yang Y;Gong T;Li X;Li C
对铂类化疗的耐药性是卵巢癌治疗中的关键问题之一。Ghrelin是一种广泛分布的肽类激素，参与了一系列的肿瘤进展。本研究的目的是确定ghrelin是否影响卵巢癌对顺铂的敏感性，并阐明其潜在机制。用人卵巢癌细胞HO-8910 PM进行体内外抗肿瘤实验。流式细胞仪检测细胞凋亡和细胞周期。Western Blot分析细胞周期蛋白的表达及信号通路。我们的研究结果表明，用ghrelin处理特异性地抑制HO-8910 PM细胞增殖，并通过S期细胞周期阻滞使这些细胞对顺铂敏感，并增强顺铂对HO-8910 PM来源的异种移植瘤体内生长的抑制作用。Ghrelin处理抑制p-Erk 1/2和p-p38的表达，这与顺铂的作用相反。而在Ghrelin作用下，顺铂对P21表达的抑制作用更强，对p-CDK 1和cyclin B1表达的上调作用更强，对细胞周期进程的阻滞作用更强。Ghrelin通过抑制p38促进S期细胞周期阻滞，上调顺铂诱导的p-CDK 1和cyclin B1表达。这项研究揭示了ghrelin通过抑制p-P38并随后促进HO-8910 PM中p-CDK 1介导的细胞周期停滞来特异性抑制铂类耐药性。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
4.3
作者：
Gillis, Laura D.;Leidal, Andrew M.;Lee, Patrick W. K.
通讯作者：
Lee, Patrick W. K.
人 iPSC-MSC 衍生的异种移植物通过抑制 Caspases 的裂解来调节免疫反应
影响因子：
5.2
作者：
Li, Cheng-Lin;Leng, Yun;Qi, Zhong-Quan
通讯作者：
Qi, Zhong-Quan
影响因子：
5.8
作者：
Gaytan, F;Barreiro, ML;Tena-Sempere, M
通讯作者：
Tena-Sempere, M
影响因子：
3.6
作者：
Garcia, Jose M.;Chen, Ji-an;Lamb, Dolores J.
通讯作者：
Lamb, Dolores J.
影响因子：
5.5
作者：
Baek, Ji Yun;Tuy An Trinh;Kang, Ki Sung
通讯作者：
Kang, Ki Sung