Cargando…

Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways

Anlotinib is a novel multi-targeted tyrosine kinase inhibitor with activity against soft tissue sarcoma, small cell lung cancer, and non-small cell lung cancer (NSCLC). Potentiating the anticancer effect of anlotinib in combination strategies remains a clinical challenge. Metformin is an oral agent...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Zhongling, Jiang, Teng, Suo, Huirong, Xu, Shan, Zhang, Cai, Ying, Guoguang, Yan, Zhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373262/
https://www.ncbi.nlm.nih.gov/pubmed/34421608
http://dx.doi.org/10.3389/fphar.2021.712181
_version_ 1783739913217245184
author Zhu, Zhongling
Jiang, Teng
Suo, Huirong
Xu, Shan
Zhang, Cai
Ying, Guoguang
Yan, Zhao
author_facet Zhu, Zhongling
Jiang, Teng
Suo, Huirong
Xu, Shan
Zhang, Cai
Ying, Guoguang
Yan, Zhao
author_sort Zhu, Zhongling
collection PubMed
description Anlotinib is a novel multi-targeted tyrosine kinase inhibitor with activity against soft tissue sarcoma, small cell lung cancer, and non-small cell lung cancer (NSCLC). Potentiating the anticancer effect of anlotinib in combination strategies remains a clinical challenge. Metformin is an oral agent that is used as a first-line therapy for type 2 diabetes. Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR). Here, we evaluated the possible synergistic effect of anlotinib and metformin in NSCLC cells. The results showed that metformin enhanced the antiproliferative effect of anlotinib. Moreover, anlotinib combined with metformin induced apoptosis and oxidative stress, which was associated with the activation of AMPK and inhibition of mTOR. Reactive oxygen species (ROS)- mediated p38/JNK MAPK and ERK signaling may be involved in the anticancer effects of this combination treatment. Our results show that metformin potentiates the efficacy of anlotinib in vivo by increasing the sensitivity of NSCLC cells to the drug. These data provide a potential rationale for the combination of anlotinib and metformin for the treatment of patients with NSCLC or other cancers.
format Online
Article
Text
id pubmed-8373262
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-83732622021-08-19 Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways Zhu, Zhongling Jiang, Teng Suo, Huirong Xu, Shan Zhang, Cai Ying, Guoguang Yan, Zhao Front Pharmacol Pharmacology Anlotinib is a novel multi-targeted tyrosine kinase inhibitor with activity against soft tissue sarcoma, small cell lung cancer, and non-small cell lung cancer (NSCLC). Potentiating the anticancer effect of anlotinib in combination strategies remains a clinical challenge. Metformin is an oral agent that is used as a first-line therapy for type 2 diabetes. Interesting, metformin also exerts broad anticancer effects through the activation of AMP-activated protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR). Here, we evaluated the possible synergistic effect of anlotinib and metformin in NSCLC cells. The results showed that metformin enhanced the antiproliferative effect of anlotinib. Moreover, anlotinib combined with metformin induced apoptosis and oxidative stress, which was associated with the activation of AMPK and inhibition of mTOR. Reactive oxygen species (ROS)- mediated p38/JNK MAPK and ERK signaling may be involved in the anticancer effects of this combination treatment. Our results show that metformin potentiates the efficacy of anlotinib in vivo by increasing the sensitivity of NSCLC cells to the drug. These data provide a potential rationale for the combination of anlotinib and metformin for the treatment of patients with NSCLC or other cancers. Frontiers Media S.A. 2021-08-04 /pmc/articles/PMC8373262/ /pubmed/34421608 http://dx.doi.org/10.3389/fphar.2021.712181 Text en Copyright © 2021 Zhu, Jiang, Suo, Xu, Zhang, Ying and Yan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhu, Zhongling
Jiang, Teng
Suo, Huirong
Xu, Shan
Zhang, Cai
Ying, Guoguang
Yan, Zhao
Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways
title Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways
title_full Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways
title_fullStr Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways
title_full_unstemmed Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways
title_short Metformin Potentiates the Effects of Anlotinib in NSCLC via AMPK/mTOR and ROS-Mediated Signaling Pathways
title_sort metformin potentiates the effects of anlotinib in nsclc via ampk/mtor and ros-mediated signaling pathways
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373262/
https://www.ncbi.nlm.nih.gov/pubmed/34421608
http://dx.doi.org/10.3389/fphar.2021.712181
work_keys_str_mv AT zhuzhongling metforminpotentiatestheeffectsofanlotinibinnsclcviaampkmtorandrosmediatedsignalingpathways
AT jiangteng metforminpotentiatestheeffectsofanlotinibinnsclcviaampkmtorandrosmediatedsignalingpathways
AT suohuirong metforminpotentiatestheeffectsofanlotinibinnsclcviaampkmtorandrosmediatedsignalingpathways
AT xushan metforminpotentiatestheeffectsofanlotinibinnsclcviaampkmtorandrosmediatedsignalingpathways
AT zhangcai metforminpotentiatestheeffectsofanlotinibinnsclcviaampkmtorandrosmediatedsignalingpathways
AT yingguoguang metforminpotentiatestheeffectsofanlotinibinnsclcviaampkmtorandrosmediatedsignalingpathways
AT yanzhao metforminpotentiatestheeffectsofanlotinibinnsclcviaampkmtorandrosmediatedsignalingpathways