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基于 Nrf2/ARE 信号通路的梓醇对肺癌细胞增殖、凋亡、迁移及氧化应激的影响。

The Impact of Catalpol on Proliferation, Apoptosis, Migration, and Oxidative Stress of Lung Cancer Cells Based on Nrf2/ARE Signaling.

机构信息

Department of Thoracic Surgery, Jiangxi Cancer Hospital of Nanchang University, Nanchang, 330029 Jiangxi, China.

Department of Thoracic Surgery, Medical College of Nanchang University, Nanchang, 330006 Jiangxi, China.

出版信息

Biomed Res Int. 2022 Jul 18;2022:5621341. doi: 10.1155/2022/5621341. eCollection 2022.

DOI:10.1155/2022/5621341
PMID:35898682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9313965/
Abstract

The effects of catalpol on lung cancer cell proliferation, apoptosis, migration, and oxidative stress via the Nrf2/ARE signaling pathway are investigated in this work. Catalpol-12 g/mL group, catalpol-24 g/mL group, catalpol-48 g/mL group, catalpol - 48 g/mL + vector group, catalpol - 48 g/mL + Nrf2 group, si-NC group, and si-Nrf2 group were used to split lung cancer cells A549 into control groups. Proliferation was detected using the CCK-8 assay; apoptosis was detected using flow cytometry; migration was detected using the transwell chamber; ROS was distinguished using the DCFHDA method; MDA, SOD, and GSH were detected using the microvolume method; and Cleaved Caspase-3, Cleaved Caspase-9, Nrf2, HO-1, MMP-9, and MMP-2 were detected using the Western blot method. Catalpol 12 g/mL and 24 g/mL-48 g/mL treatment decreased the proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells when compared to the control group. SOD and GSH levels of lung cancer cells were decreased, and MDA and ROS levels were increased. Cleaved caspase-3, cleaved caspase-9 protein expression levels, and apoptosis were boosted ( < 0.05). The proliferation activity, migration number, and protein levels of Nrf2, HO-1, MMP-9, and MMP-2 in the catalpol - 48 g/mL + Nrf2 group were raised compared to the catalpol - 48 g/mL + vector group, whereas there was an apparent drop in the Cleaved Caspase-3, Cleaved Caspase-9, and apoptosis rate. Similarly, SOD and GSH contents increased, whereas MDA and ROS decreased ( < 0.05). The proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells in the si-Nrf2 group were all decreased when compared to the si-NC and control groups. Cleaved Caspase-3 and Cleaved Caspase-9 protein expression, on the other hand, increased as MDA and ROS levels were raised while SOD and GSH levels dropped ( < 0.05). It reveals that catalpol inhibits the Nrf2/ARE signaling pathway, which causes antiproliferation, migration, apoptosis, and oxidative stress in cancer cells of lungs. The rate of apoptosis was also lowered.

摘要

本研究旨在探讨梓醇通过 Nrf2/ARE 信号通路对肺癌细胞增殖、凋亡、迁移和氧化应激的影响。将肺癌细胞 A549 分为对照组、梓醇-12g/mL 组、梓醇-24g/mL 组、梓醇-48g/mL 组、梓醇-48g/mL+载体组、梓醇-48g/mL+Nrf2 组、si-NC 组和 si-Nrf2 组。采用 CCK-8 法检测细胞增殖;采用流式细胞术检测细胞凋亡;采用 Transwell 小室检测细胞迁移;采用 DCFHDA 法区分 ROS;采用微量法检测 MDA、SOD 和 GSH;采用 Western blot 法检测 Cleaved Caspase-3、Cleaved Caspase-9、Nrf2、HO-1、MMP-9 和 MMP-2 蛋白水平。与对照组相比,梓醇 12g/mL 和 24g/mL-48g/mL 处理降低了肺癌细胞的增殖活性、迁移数量和 Nrf2、HO-1、MMP-9 和 MMP-2 蛋白水平。肺癌细胞 SOD 和 GSH 水平降低,MDA 和 ROS 水平升高。Cleaved caspase-3、Cleaved caspase-9 蛋白表达水平和细胞凋亡率增加(<0.05)。与梓醇-48g/mL+载体组相比,梓醇-48g/mL+Nrf2 组的增殖活性、迁移数量和 Nrf2、HO-1、MMP-9 和 MMP-2 蛋白水平升高,Cleaved Caspase-3、Cleaved Caspase-9 和细胞凋亡率明显降低。同样,SOD 和 GSH 含量增加,MDA 和 ROS 减少(<0.05)。与 si-NC 和对照组相比,si-Nrf2 组肺癌细胞的增殖活性、迁移数量和 Nrf2、HO-1、MMP-9 和 MMP-2 蛋白水平均降低。Cleaved Caspase-3 和 Cleaved Caspase-9 蛋白表达水平升高,MDA 和 ROS 水平升高,SOD 和 GSH 水平降低(<0.05)。结果表明,梓醇通过抑制 Nrf2/ARE 信号通路抑制肺癌细胞增殖、迁移、凋亡和氧化应激,从而降低细胞凋亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/17767e727320/BMRI2022-5621341.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/f316af1ef1eb/BMRI2022-5621341.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/25d14478278d/BMRI2022-5621341.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/e71e4f559f4f/BMRI2022-5621341.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/319fd4d913b3/BMRI2022-5621341.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/61638784f708/BMRI2022-5621341.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/17767e727320/BMRI2022-5621341.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/f316af1ef1eb/BMRI2022-5621341.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/25d14478278d/BMRI2022-5621341.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/e71e4f559f4f/BMRI2022-5621341.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/319fd4d913b3/BMRI2022-5621341.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/61638784f708/BMRI2022-5621341.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6179/9313965/17767e727320/BMRI2022-5621341.006.jpg

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