Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC) is the third most common malignant neo...

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Main Authors: Su M, Qin B, Liu F, Chen Y, Zhang R
Format: Article
Language:English
Published: Dove Medical Press 2017-11-01
Series:Drug Design, Development and Therapy
Subjects:
Online Access:https://www.dovepress.com/andrographolide-enhanced-5-fluorouracil-induced-antitumor-effect-in-co-peer-reviewed-article-DDDT
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spelling doaj-07109d6da3504e68a672f1701a87af912020-11-24T22:38:52ZengDove Medical PressDrug Design, Development and Therapy1177-88812017-11-01Volume 113333334135710Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathwaySu MQin BLiu FChen YZhang RMeng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu) is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro) is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET) was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-METhttps://www.dovepress.com/andrographolide-enhanced-5-fluorouracil-induced-antitumor-effect-in-co-peer-reviewed-article-DDDTAndro5-FuHCT-116 cellsapoptosisp-MET
collection DOAJ
language English
format Article
sources DOAJ
author Su M
Qin B
Liu F
Chen Y
Zhang R
spellingShingle Su M
Qin B
Liu F
Chen Y
Zhang R
Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway
Drug Design, Development and Therapy
Andro
5-Fu
HCT-116 cells
apoptosis
p-MET
author_facet Su M
Qin B
Liu F
Chen Y
Zhang R
author_sort Su M
title Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway
title_short Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway
title_full Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway
title_fullStr Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway
title_full_unstemmed Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway
title_sort andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-met pathway
publisher Dove Medical Press
series Drug Design, Development and Therapy
issn 1177-8881
publishDate 2017-11-01
description Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu) is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro) is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET) was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-MET
topic Andro
5-Fu
HCT-116 cells
apoptosis
p-MET
url https://www.dovepress.com/andrographolide-enhanced-5-fluorouracil-induced-antitumor-effect-in-co-peer-reviewed-article-DDDT
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