Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation.
Colorectal cancer (CRC) is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but n...
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doaj-0089b313f1ef4f52aab09e46d5f3318b2020-11-24T21:50:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9778110.1371/journal.pone.0097781Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation.Xinbing SuiYinghua XuJie YangYong FangHaizhou LouWeidong HanMaolin ZhangWei ChenKaifeng WangDa LiWei JinFang LouYu ZhengHong HuLiu GongXiaoyun ZhouQin PanHongming PanXian WangChao HeColorectal cancer (CRC) is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation.http://europepmc.org/articles/PMC4029793?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xinbing Sui Yinghua Xu Jie Yang Yong Fang Haizhou Lou Weidong Han Maolin Zhang Wei Chen Kaifeng Wang Da Li Wei Jin Fang Lou Yu Zheng Hong Hu Liu Gong Xiaoyun Zhou Qin Pan Hongming Pan Xian Wang Chao He |
spellingShingle |
Xinbing Sui Yinghua Xu Jie Yang Yong Fang Haizhou Lou Weidong Han Maolin Zhang Wei Chen Kaifeng Wang Da Li Wei Jin Fang Lou Yu Zheng Hong Hu Liu Gong Xiaoyun Zhou Qin Pan Hongming Pan Xian Wang Chao He Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. PLoS ONE |
author_facet |
Xinbing Sui Yinghua Xu Jie Yang Yong Fang Haizhou Lou Weidong Han Maolin Zhang Wei Chen Kaifeng Wang Da Li Wei Jin Fang Lou Yu Zheng Hong Hu Liu Gong Xiaoyun Zhou Qin Pan Hongming Pan Xian Wang Chao He |
author_sort |
Xinbing Sui |
title |
Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. |
title_short |
Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. |
title_full |
Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. |
title_fullStr |
Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. |
title_full_unstemmed |
Use of metformin alone is not associated with survival outcomes of colorectal cancer cell but AMPK activator AICAR sensitizes anticancer effect of 5-fluorouracil through AMPK activation. |
title_sort |
use of metformin alone is not associated with survival outcomes of colorectal cancer cell but ampk activator aicar sensitizes anticancer effect of 5-fluorouracil through ampk activation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Colorectal cancer (CRC) is still the third most common cancer and the second most common causes of cancer-related death around the world. Metformin, a biguanide, which is widely used for treating diabetes mellitus, has recently been shown to have a suppressive effect on CRC risk and mortality, but not all laboratory studies suggest that metformin has antineoplastic activity. Here, we investigated the effect of metformin and AMPK activator AICAR on CRC cells proliferation. As a result, metformin did not inhibit cell proliferation or induce apoptosis for CRC cell lines in vitro and in vivo. Different from metformin, AICAR emerged antitumor activity and sensitized anticancer effect of 5-FU on CRC cells in vitro and in vivo. In further analysis, we show that AMPK activation may be a key molecular mechanism for the additive effect of AICAR. Taken together, our results suggest that metformin has not antineoplastic activity for CRC cells as a single agent but AMPK activator AICAR can induce apoptosis and enhance the cytotoxic effect of 5-FU through AMPK activation. |
url |
http://europepmc.org/articles/PMC4029793?pdf=render |
work_keys_str_mv |
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