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卡维地洛通过抑制 ROS 介导的 PI3K/AKT 信号通路抑制乳腺上皮细胞的恶性增殖。

Carvedilol suppresses malignant proliferation of mammary epithelial cells through inhibition of the ROS‑mediated PI3K/AKT signaling pathway.

机构信息

The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.

Qilu Children's Hospital of Shandong University, Jinan, Shandong 250040, P.R. China.

出版信息

Oncol Rep. 2019 Feb;41(2):811-818. doi: 10.3892/or.2018.6873. Epub 2018 Nov 19.

DOI:10.3892/or.2018.6873
PMID:30483797
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6312993/
Abstract

Reactive oxygen species (ROS) cause oncogenic mutations through direct interaction with DNA. Carvedilol (CAR) exhibits antioxidative activity, and pre‑clinical studies have identified that CAR may prevent malignant transformation in certain carcinogenic models. This suggests that CAR may be a potential agent in cancer prevention. In the present study, non‑cancerous MCF‑10A cells were used as a model to investigate the chemopreventive effect of CAR on benzo(a)pyrene (BaP)‑induced cellular carcinogenesis. It was identified that CAR had the ability to eliminate BaP‑induced ROS production and subsequent DNA damage. CAR/BaP activated the ROS‑mediated phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT)Thr308 signaling pathway, whereas the effectors of the PI3K/AKT signaling pathway, murine double minute 2 (MDM2) and p53Ser15, served important functions in the BaP/CAR‑mediated MCF10A cellular transformation. The results of the present study indicated that CAR may be a novel chemopreventive agent, notably in the prevention of estrogen receptor‑negative breast cancer. The antioxidant effects of CAR may contribute to its chemopreventive activity.

摘要

活性氧（ROS）通过与 DNA 的直接相互作用导致致癌突变。卡维地洛（CAR）具有抗氧化活性，临床前研究表明 CAR 可能在某些致癌模型中预防恶性转化。这表明 CAR 可能是一种潜在的癌症预防剂。在本研究中，使用非癌性 MCF-10A 细胞作为模型，研究 CAR 对苯并（a）芘（BaP）诱导的细胞癌变的化学预防作用。结果表明，CAR 具有消除 BaP 诱导的 ROS 产生和随后的 DNA 损伤的能力。CAR/BaP 激活了 ROS 介导的磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（AKT）Thr308 信号通路，而 PI3K/AKT 信号通路的效应物，鼠双微体 2（MDM2）和 p53Ser15，在 BaP/CAR 介导的 MCF10A 细胞转化中发挥重要作用。本研究结果表明，CAR 可能是一种新型的化学预防剂，特别是在预防雌激素受体阴性乳腺癌方面。CAR 的抗氧化作用可能有助于其化学预防活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/f2ab3fbb6d08/OR-41-02-0811-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/8aa7af860b9c/OR-41-02-0811-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/5a045454c5bc/OR-41-02-0811-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/7b95dca50114/OR-41-02-0811-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/128c9db3b75b/OR-41-02-0811-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/2e66ac9a7752/OR-41-02-0811-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/f2ab3fbb6d08/OR-41-02-0811-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/8aa7af860b9c/OR-41-02-0811-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/5a045454c5bc/OR-41-02-0811-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/7b95dca50114/OR-41-02-0811-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/128c9db3b75b/OR-41-02-0811-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/2e66ac9a7752/OR-41-02-0811-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6af/6312993/f2ab3fbb6d08/OR-41-02-0811-g05.jpg

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