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大黄素甲醚8 - O - β - 吡喃葡萄糖苷通过调控lnc - SLC4A1 - 1/H3K27ac/NF - κB信号通路发挥对 Ishikawa 细胞的抑癌作用。

Physcion 8-O-β-glucopyranoside exerts carcinostasis ability in Ishikawa cells via regulating lnc-SLC4A1-1/H3K27ac/NF-κB pathway.

作者信息

Yang Lili

机构信息

Department of Obstetrics and Gynecology, Taizhou People's Hospital, Taizhou, Jiangsu, China;, Email:

出版信息

Pharmazie. 2020 Jul 1;75(7):348-352. doi: 10.1691/ph.2020.9608.

Abstract

This study aimed to investigate whether physcion 8-O-β-glucopyranoside (PG) exerted anti-tumor effects in endometrial cancer cells regulating the long non-coding RNA lnc-SLC4A1-1. The anti-tumor effects of PG on endometrial cancer by evaluating Ishikawa cell growth and metastasis, and the expression of lnc-SLC4A1-1 was determined after PG treatment. Subsequently, the role and regulatory mechanism of lnc-SLC4A1-1 dysregulation in PG-treated endometrial cancer cells were explored. PG treatment resulted in dramatical depression of cell viability, remarkable promotion of cell apoptosis and dramatic suppression of migration and invasion in Ishikawa cells in a dose-dependent way. Moreover, PG decreased the level of lnc-SLC4A1-1, and high levels of lnc-SLC4A1-1 reversed the effects of PG on Ishikawa cells. Furthermore, lnc-SLC4A1-1 was transcriptionally activated by H3K27ac and interacted with NF-κB p65 in Ishikawa cells. PG treatment depressed the NF-κB signal in Ishikawa cells, which were significantly reversed after overexpression of lnc-SLC4A1-1. Our results indicate that PG exerts anti-tumor activity in endometrial cancer cells. Lnc-SLC4A1-1/H3K27ac/NF-κB pathway may be a possible mechanism to mediate the anti-tumor effects of PG, which provide a promising targeted strategy for treatment of endometrial cancer.

摘要

本研究旨在探讨大黄素甲醚8 - O - β - 吡喃葡萄糖苷(PG)是否通过调节长链非编码RNA lnc - SLC4A1 - 1在子宫内膜癌细胞中发挥抗肿瘤作用。通过评估PG对Ishikawa细胞生长和转移的影响来研究其对子宫内膜癌的抗肿瘤作用,并在PG处理后测定lnc - SLC4A1 - 1的表达。随后,探讨lnc - SLC4A1 - 1失调在PG处理的子宫内膜癌细胞中的作用及调控机制。PG处理导致Ishikawa细胞活力显著降低,细胞凋亡显著增加,迁移和侵袭显著受到抑制,且呈剂量依赖性。此外,PG降低了lnc - SLC4A1 - 1的水平,而高水平的lnc - SLC4A1 - 1可逆转PG对Ishikawa细胞的作用。此外,lnc - SLC4A1 - 1在Ishikawa细胞中被H3K27ac转录激活并与NF - κB p65相互作用。PG处理抑制了Ishikawa细胞中的NF - κB信号,lnc - SLC4A1 - 1过表达后该信号显著逆转。我们的结果表明,PG在子宫内膜癌细胞中发挥抗肿瘤活性。Lnc - SLC4A1 - 1/H3K27ac/NF - κB通路可能是介导PG抗肿瘤作用的一种潜在机制,这为子宫内膜癌的治疗提供了一种有前景的靶向策略。

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