|Table of Contents|

Metformin may induce autophagy of breast cancer cells by mTOR signaling pathway

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 20
Page:
3764-3770
Research Field:
Publishing date:

Info

Title:
Metformin may induce autophagy of breast cancer cells by mTOR signaling pathway
Author(s):
LI Shaojun1; 2; ZHAO Yihan3; GAO Xiao1; ZHANG Xin1; GUO Aining1; LIU Di1; DIAO Yan1; ZHANG Shuqun1; MIN Weili1
1.Department of Oncology,the Second Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710004,China;2.Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China；3.Hospital of Stomatology,Xi'an Jiaotong University,Shaanxi Xi'an 710004,China.
Keywords:
breast cancer; metformin; autophagy; AMPK/mTOR signaling pathway; PI3K/AKT/mTOR signaling pathway
PACS:
R737.9
DOI:
10.3969/j.issn.1672-4992.2023.20.008
Abstract:
Objective：To investigate whether metformin can induce autophagy of breast cancer cells and inhibit tumor growth through mammalian target of rapamycin (mTOR) pathway.Methods：Three kinds of breast cancer cells,MCF-7,MDA-MB-231 and SK-BR-3,were cultured and treated with different concentrations of metformin for 24~72 hours.The autophagy of cancer cells was detected by CCK8,TUNEL,autophagosome test,electron microscope,immunofluorescence and Western blotting.Results:Metformin could inhibit the proliferation of MCF-7,MDA-MB-231 and SK-BR-3 tumor cells.With the increase of metformin concentration and action time,and cancer cells inhibitory ability was enhanced.Metformin could promote the production of autophagosomes and apoptosis of MCF-7 tumor cells.The expression of p-AMPK was increased but the expression of p-PI3K,p-AKT and p-mTOR was decreased after MCF-7 cells were given metformin,compared with the control group.Compared with the metformin group,the expression of p-AMPK was decreased,the expression of p-PI3K and p-AKT was unchanged,and p-mTOR expression was increased after MCF-7 cells were given metformin+AMPK inhibitor.After the MCF-7 cells were given metformin+PI3K agonist,compared with the metformin group,p-AMPK expression remained unchanged,the expression of p-PI3K and p-AKT was increased,and p-mTOR expression was increased.After MCF-7 cells were given metformin+AKT agonist,compared with metformin group,the expression of p-AMPK and p-PI3K was unchanged,the expression of p-AKT was increased,and the expression of p-mTOR was increased.Conclusion:Metformin may induce autophagy and apoptosis of breast cancer cells MCF-7 by activating AMPK/mTOR and inhibiting PI3K/AKT/mTOR signaling pathway,thus inhibiting the proliferation of cancer cells.

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Memo

Memo:
陕西省国际科技合作重点项目计划项目(编号：2019KW-035)；陕西省中西医结合肿瘤防治重点实验室建设项目(编号：2022-ZXY-SYS-002)；西安交通大学第二附属医院院基金自由探索［编号：2020YJ(ZYTS)611］；西安交通大学第二附属医院新技术（编号：2018-56）
Last Update: 1900-01-01