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胸腺肽 β4 衍生肽对卵巢癌细胞迁移和侵袭的影响。

Effects of thymosin β4-derived peptides on migration and invasion of ovarian cancer cells.

机构信息

Department of Medicine, Pusan National University School of Medicine, Pusan National University Hospital, Busan, South Korea.

Department of Obstetrics and Gynecology, Kosin University College of Medicine, Busan, South Korea.

出版信息

Genes Genomics. 2021 Aug;43(8):987-993. doi: 10.1007/s13258-021-01127-7. Epub 2021 Jun 25.

Abstract

BACKGROUND

Thymosin β4 (Tβ4) is a highly conserved actin binding protein associated with the metastatic potential of tumor cells by stimulating cell migration. The role of Tβ4 and its derived fragment peptides in migration of ovarian cancer cells has not been studied.

OBJECTIVE

To analyze the effects of Tβ4 and its derived fragment peptides on ovarian cancer cell migration and invasion, we applied Tβ4 and three Tβ4-derived synthetic peptides to SKOV3 ovarian cancer cells.

METHOD

The migration and invasion of SKOV3 cells treated with Tβ4(1-43), Tβ4(1-15), Tβ4(12-26), Tβ4(23-), and untreated control were analyzed by in vitro migration and invasion assay with transwell plate. Cell proliferation assay was conducted to identify the effect of Tβ4 and its derived peptide on SKOV3 cell proliferation. The expression of Tβ4 related proteins related with cell proliferation was analyzed by Western blot after treatment with Tβ4 and its derived peptides.

RESULTS

Cell migration and invasion were significantly increased in Tβ4 peptide-treated SKOV3 cells compared with untreated control. All three Tβ4-derived fragment peptides including those without an actin binding site significantly stimulated migration and invasion of SKOV3 cells. Tβ4 and its derived peptide significantly stimulated SKOV3 cell proliferation and up-regulated the expression of RACK-1 protein.

CONCLUSIONS

The Tβ4 peptide and all of its derived fragment peptides including those without an actin binding motif stimulate migration and invasion of SKOV3 ovarian cancer cells. All peptides significantly increased RACK-1 expression and cell proliferation of SKOV3 cells. These results suggest that Tβ4 stimulates migration and invasion of SKOV3 cells by stimulation of cell proliferation through up-regulation of RACK-1 protein.

摘要

背景

胸腺素β4(Tβ4)是一种高度保守的肌动蛋白结合蛋白,通过刺激细胞迁移与肿瘤细胞的转移潜能相关。Tβ4 及其衍生肽段在卵巢癌细胞迁移中的作用尚未被研究。

目的

分析 Tβ4 及其衍生肽段对卵巢癌细胞迁移和侵袭的影响,我们应用 Tβ4 和三种 Tβ4 衍生的合成肽段处理 SKOV3 卵巢癌细胞。

方法

通过体外迁移和侵袭试验用 Transwell 板分析 Tβ4(1-43)、Tβ4(1-15)、Tβ4(12-26)、Tβ4(23-)和未经处理的对照 SKOV3 细胞的迁移和侵袭。通过细胞增殖试验确定 Tβ4 及其衍生肽对 SKOV3 细胞增殖的影响。用 Tβ4 和其衍生肽处理后,通过 Western blot 分析与细胞增殖相关的 Tβ4 相关蛋白的表达。

结果

与未经处理的对照相比,Tβ4 肽处理的 SKOV3 细胞的迁移和侵袭明显增加。所有三种 Tβ4 衍生的片段肽,包括没有肌动蛋白结合位点的肽,均显著刺激 SKOV3 细胞的迁移和侵袭。Tβ4 和其衍生肽显著刺激 SKOV3 细胞增殖并上调 RACK-1 蛋白的表达。

结论

Tβ4 肽及其所有衍生的片段肽(包括没有肌动蛋白结合基序的肽)均刺激 SKOV3 卵巢癌细胞的迁移和侵袭。所有肽均显著增加 SKOV3 细胞 RACK-1 表达和增殖。这些结果表明,Tβ4 通过上调 RACK-1 蛋白刺激细胞增殖来刺激 SKOV3 细胞的迁移和侵袭。

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