Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer

To explore the therapeutic effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer and the mechanism involved. In vitro cell test: the cytotoxicity of metformin under different oxygen and glucose contents was evaluated using cell survival curves. In vi...

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Main Authors: LI Huichao, ZHAO Mingjuan, TIAN Long
Format: Article
Language:zho
Published: Science Press 2022-12-01
Series:Fushe yanjiu yu fushe gongyi xuebao
Subjects:
Online Access:http://www.fs.sinap.ac.cn/thesisDetails#10.11889/j.1000-3436.2022-0040&lang=zh
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author LI Huichao
ZHAO Mingjuan
TIAN Long
author_facet LI Huichao
ZHAO Mingjuan
TIAN Long
author_sort LI Huichao
collection DOAJ
description To explore the therapeutic effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer and the mechanism involved. In vitro cell test: the cytotoxicity of metformin under different oxygen and glucose contents was evaluated using cell survival curves. In vivo xenograft tumor test: NSCLC-A549 cells were injected into mice, which were then divided into the following five groups: control group, metformin group, single high-dose radiotherapy group, metformin 1 h before radiotherapy group, and metformin 24 h after radiotherapy group. Growth of the tumor was evaluated in each group, and the blood flow and histology of the tumor tissues were analyzed. According to the in vitro test results, metformin was the most cytotoxic under hypoxic and low-glucose conditions. The in vivo results showed that the tumor volume was the smallest in the mouse groups administered metformin 1 h before high-dose radiotherapy and 24 h after radiotherapy ((0.47±0.12) cm3 and (0.49±0.21) cm3, respectively). Blood flow analysis showed that single high-dose radiotherapy destroyed the micro-vessels of tumor tissue and reduced the perfusion of oxygen and glucose. Histological analysis revealed that cells in hypoxic and hypoglycemic area of the tumor tissue center were preferentially killed by metformin, whereas there were viable cells in the surrounding well perfused areas. Metformin combined with single high-dose radiotherapy enhanced the toxicity by changing tumor cell metabolism. These results provide theoretical and data support for the future use of metformin combined with stereotactic body radiotherapy.
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spelling doaj.art-c2ad8c3eb59e4ac88a9f78bf85aeb1f52023-02-07T07:42:32ZzhoScience PressFushe yanjiu yu fushe gongyi xuebao1000-34362022-12-01406232810.11889/j.1000-3436.2022-00401000-3436(2022)06-0023-06Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancerLI Huichao0ZHAO Mingjuan1TIAN Long2The First Affiliated Hospital of Hebei Northern University, Zhangjiakou 075000, ChinaHebei General Hospital, Shijiazhuang 050000, ChinaThe First Affiliated Hospital of Hebei Northern University, Zhangjiakou 075000, ChinaTo explore the therapeutic effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer and the mechanism involved. In vitro cell test: the cytotoxicity of metformin under different oxygen and glucose contents was evaluated using cell survival curves. In vivo xenograft tumor test: NSCLC-A549 cells were injected into mice, which were then divided into the following five groups: control group, metformin group, single high-dose radiotherapy group, metformin 1 h before radiotherapy group, and metformin 24 h after radiotherapy group. Growth of the tumor was evaluated in each group, and the blood flow and histology of the tumor tissues were analyzed. According to the in vitro test results, metformin was the most cytotoxic under hypoxic and low-glucose conditions. The in vivo results showed that the tumor volume was the smallest in the mouse groups administered metformin 1 h before high-dose radiotherapy and 24 h after radiotherapy ((0.47±0.12) cm3 and (0.49±0.21) cm3, respectively). Blood flow analysis showed that single high-dose radiotherapy destroyed the micro-vessels of tumor tissue and reduced the perfusion of oxygen and glucose. Histological analysis revealed that cells in hypoxic and hypoglycemic area of the tumor tissue center were preferentially killed by metformin, whereas there were viable cells in the surrounding well perfused areas. Metformin combined with single high-dose radiotherapy enhanced the toxicity by changing tumor cell metabolism. These results provide theoretical and data support for the future use of metformin combined with stereotactic body radiotherapy.http://www.fs.sinap.ac.cn/thesisDetails#10.11889/j.1000-3436.2022-0040&lang=zhnon-small cell lung cancermetforminsingle high-dose radiotherapyaction mechanism
spellingShingle LI Huichao
ZHAO Mingjuan
TIAN Long
Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer
Fushe yanjiu yu fushe gongyi xuebao
non-small cell lung cancer
metformin
single high-dose radiotherapy
action mechanism
title Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer
title_full Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer
title_fullStr Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer
title_full_unstemmed Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer
title_short Study on the therapeutic mechanism and effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer
title_sort study on the therapeutic mechanism and effect of metformin combined with single high dose radiotherapy in mice with non small cell lung cancer
topic non-small cell lung cancer
metformin
single high-dose radiotherapy
action mechanism
url http://www.fs.sinap.ac.cn/thesisDetails#10.11889/j.1000-3436.2022-0040&lang=zh
work_keys_str_mv AT lihuichao studyonthetherapeuticmechanismandeffectofmetformincombinedwithsinglehighdoseradiotherapyinmicewithnonsmallcelllungcancer
AT zhaomingjuan studyonthetherapeuticmechanismandeffectofmetformincombinedwithsinglehighdoseradiotherapyinmicewithnonsmallcelllungcancer
AT tianlong studyonthetherapeuticmechanismandeffectofmetformincombinedwithsinglehighdoseradiotherapyinmicewithnonsmallcelllungcancer