七叶皂苷通过抑制核因子-κB 的激活来抑制白细胞介素-8 和血管内皮生长因子的产生,从而抑制胰腺癌细胞系的血管生成。

Escin inhibits angiogenesis by suppressing interleukin‑8 and vascular endothelial growth factor production by blocking nuclear factor‑κB activation in pancreatic cancer cell lines.

机构信息

Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.

出版信息

Oncol Rep. 2021 May;45(5). doi: 10.3892/or.2021.8006. Epub 2021 Mar 24.

Abstract

Pancreatic cancer (PaCa) is one of the most aggressive types of cancer. Thus, the development of new and more effective therapies is urgently required. Escin, a pentacyclic triterpenoid from the horse chestnut, has been reported to exhibit antitumor potential by reducing cell proliferation and blocking the nuclear factor‑κB (NF‑κB) signaling pathway in several types of cancer. Our previous study reported that NF‑κB enhanced the secretion of interleukin (IL)‑8 and vascular endothelial growth factor (VEGF), thereby inducing angiogenesis in PaCa cell lines. In the present study, it was examined whether escin inhibited angiogenesis by blocking NF‑κB activation in PaCa. It was initially confirmed that escin, at concentrations >10 µM, significantly inhibited the proliferation of several PaCa cell lines. Next, using immunocytochemical staining, it was found that escin inhibited the nuclear translocation of NF‑κB. Furthermore, ELISA confirmed that NF‑κB activity in the escin‑treated PaCa cells was significantly inhibited and reverse transcription‑quantitative PCR showed that the mRNA expression levels of tumor necrosis factor‑α‑induced and were significantly suppressed following escin treatment in the PaCa cell lines. ELISA also showed that escin decreased the secretion of IL‑8 and VEGF from the PaCa cells. Furthermore, tube formation in immortalized human endothelial cells was inhibited following incubation with the supernatants from escin‑treated PaCa cells. These results indicated that escin inhibited angiogenesis by reducing the secretion of IL‑8 and VEGF by blocking NF‑κB activity in PaCa. In conclusion, escin could be used as a novel molecular therapy for PaCa.

摘要

胰腺癌(PaCa)是最具侵袭性的癌症之一。因此,迫切需要开发新的、更有效的治疗方法。七叶皂苷是从欧洲七叶树中提取的一种五环三萜皂苷,已被报道通过减少细胞增殖和阻断几种类型的癌症中的核因子-κB(NF-κB)信号通路来发挥抗肿瘤作用。我们之前的研究报告称,NF-κB 增强白细胞介素(IL)-8 和血管内皮生长因子(VEGF)的分泌,从而诱导 PaCa 细胞系中的血管生成。在本研究中,研究了七叶皂苷是否通过阻断 NF-κB 激活来抑制 PaCa 中的血管生成。最初证实,浓度>10 μM 的七叶皂苷可显著抑制几种 PaCa 细胞系的增殖。接下来,通过免疫细胞化学染色发现,七叶皂苷抑制了 NF-κB 的核易位。此外,ELISA 证实 NF-κB 活性在七叶皂苷处理的 PaCa 细胞中显著受到抑制,逆转录-定量 PCR 显示在 PaCa 细胞系中用七叶皂苷处理后,肿瘤坏死因子-α诱导的 和 的 mRNA 表达水平显著受到抑制。ELISA 还显示,七叶皂苷可减少 PaCa 细胞中 IL-8 和 VEGF 的分泌。此外,用七叶皂苷处理过的 PaCa 细胞的上清液孵育后,可抑制永生化人内皮细胞的管形成。这些结果表明,七叶皂苷通过抑制 NF-κB 活性来减少 PaCa 中 IL-8 和 VEGF 的分泌来抑制血管生成。总之,七叶皂苷可作为治疗 PaCa 的新型分子疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac1/7962110/21d1be3ce5b8/or-45-05-8006-g00.jpg

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