Abstract

Introduction

The expression levels of signal transducer and activator of transcription 3 (STAT3) protein and Fascin-1 were inhibited using the STAT3 inhibitor BP-1-102 and RNA interference, respectively, to investigate the expression of AtT20 in mouse pituitary cells. The proliferative capacity and related molecular mechanisms of pituitary tumor cells were then analyzed.

Methods

Mouse AtT20 pituitary adenoma cells were divided into a control group (Pa group), a STAT3 inhibitor vehicle group (PA + DMSO group), a STAT3 inhibitor group (PA + BP-1-102 group), a Fascin-1 negative control group (PA + neg-siRNA group) and a Fascin-1 silenced group (PA + Fascin-siRNA group). The related protein expression and cell proliferation of the five groups were measured using immunofluorescence, Western blot and real-time RT-PCR, whereas their apoptosis and cell cycle were evaluated using CCK-8 and flow cytometry.

Results

Proliferation of AtT20 cells is inhibited with BP-1-102 enhanced apoptosis, at the same time reduced the expression of Fascin-1 and N-cadherin, and increased the expression of E-cadherin. After inhibiting Fascin-1, the expression of STAT3 decreased, the expression of N-cadherin decreased and the expression of E-cadherin increased.

Conclusions

BP-1-102 is a novel drug with a great potential in pituitary tumors. Given their important roles in the growth of pituitary adenomas, STAT3 and Fascin-1 can be used as new treatment targets.

中文翻译：

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BP-1-102 和通过 RNA 干扰沉默 Fascin-1 通过信号转导和转录激活因子 3/fascin-1 通路抑制小鼠垂体腺瘤 AtT20 细胞的增殖

摘要

介绍

分别使用 STAT3 抑制剂 BP-1-102 和 RNA 干扰抑制信号转导和转录激活因子 3 (STAT3) 蛋白和 Fascin-1 的表达水平，以研究 AtT20 在小鼠垂体细胞中的表达。然后分析垂体肿瘤细胞的增殖能力和相关分子机制。

方法

将小鼠AtT20垂体腺瘤细胞分为对照组（Pa组）、STAT3抑制剂载体组（PA+DMSO组）、STAT3抑制剂组（PA+BP-1-102组）、Fascin-1阴性对照组（PA + neg-siRNA 组）和 Fascin-1 沉默组（PA + Fascin-siRNA 组）。使用免疫荧光、Western印迹和实时RT-PCR检测5组相关蛋白表达和细胞增殖，而使用CCK-8和流式细胞术评估它们的细胞凋亡和细胞周期。

结果

BP-1-102增强细胞凋亡抑制AtT20细胞增殖，同时降低Fascin-1和N-cadherin的表达，增加E-cadherin的表达。抑制Fascin-1后，STAT3表达降低，N-cadherin表达降低，E-cadherin表达升高。

结论

BP-1-102是一种在垂体瘤中具有巨大潜力的新型药物。鉴于它们在垂体腺瘤生长中的重要作用，STAT3 和 Fascin-1 可用作新的治疗靶点。