YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice
Dasatinib, as a second-generation broad-spectrum tyrosine kinase inhibitor, presents an antitumor effect by inhibiting tyrosine kinases. However, dasatinib causes serious side effects, such as gastrointestinal bleeding and liver toxicity, possibly through the activation of ROCK kinase and MLC phosph...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2020-01-01
|
Series: | Evidence-Based Complementary and Alternative Medicine |
Online Access: | http://dx.doi.org/10.1155/2020/4646029 |
id |
doaj-2960a83f00d44e6ea1154def4c16de1c |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuankai Liu Yujie Dai Han Xu Qianliu Zhou Fang Li Boyang Yu Yuanyuan Zhang Junping Kou |
spellingShingle |
Yuankai Liu Yujie Dai Han Xu Qianliu Zhou Fang Li Boyang Yu Yuanyuan Zhang Junping Kou YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice Evidence-Based Complementary and Alternative Medicine |
author_facet |
Yuankai Liu Yujie Dai Han Xu Qianliu Zhou Fang Li Boyang Yu Yuanyuan Zhang Junping Kou |
author_sort |
Yuankai Liu |
title |
YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice |
title_short |
YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice |
title_full |
YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice |
title_fullStr |
YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice |
title_full_unstemmed |
YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in Mice |
title_sort |
yqfm alleviates side effects caused by dasatinib through the rock/mlc pathway in mice |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2020-01-01 |
description |
Dasatinib, as a second-generation broad-spectrum tyrosine kinase inhibitor, presents an antitumor effect by inhibiting tyrosine kinases. However, dasatinib causes serious side effects, such as gastrointestinal bleeding and liver toxicity, possibly through the activation of ROCK kinase and MLC phosphorylation. At present, there is no effective prevention and treatment method. Previous research studies have shown that YQFM (YiQiFuMai powder injection) protects the blood-brain barrier by inhibiting the ROCK/MLC signaling pathway; whether YQFM can alleviate the side effects of dasatinib is unknown. In this study, dasatinib was injected (i.p. 70 mg/kg) and YQFM (i.p. 0.336 g/kg, 0.672 g/kg, 1.342 g/kg) was given in advance for 3 days to mice, to explore the effect of YQFM on side effects induced by Dasatinib. The results confirmed that YQFM significantly decreased Evans blue leakage in the small intestine and increased intestinal blood flow, increased the expression of ZO-1, Occludin, and VE-cadherin, and reduced the contents of D-lactic acid, s-VE-cadherin, Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) in serum. Finally, YQFM inhibited the expression of ROCK-1 and phosphorylation of MLC induced by Dasatinib. These findings suggested that YQFM could improve the side effects caused by Dasatinib linked with the ROCK/MLC signaling pathway, as shown in the graphical abstract. |
url |
http://dx.doi.org/10.1155/2020/4646029 |
work_keys_str_mv |
AT yuankailiu yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice AT yujiedai yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice AT hanxu yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice AT qianliuzhou yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice AT fangli yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice AT boyangyu yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice AT yuanyuanzhang yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice AT junpingkou yqfmalleviatessideeffectscausedbydasatinibthroughtherockmlcpathwayinmice |
_version_ |
1715359892519256064 |
spelling |
doaj-2960a83f00d44e6ea1154def4c16de1c2020-11-25T02:53:10ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882020-01-01202010.1155/2020/46460294646029YQFM Alleviates Side Effects Caused by Dasatinib through the ROCK/MLC Pathway in MiceYuankai Liu0Yujie Dai1Han Xu2Qianliu Zhou3Fang Li4Boyang Yu5Yuanyuan Zhang6Junping Kou7Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaJiangsu Key Laboratory of TCM Evaluation and Translational Research, Research Center for Traceability and Standardization of TCMs, Department of Pharmacology of Chinese Material Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, ChinaDasatinib, as a second-generation broad-spectrum tyrosine kinase inhibitor, presents an antitumor effect by inhibiting tyrosine kinases. However, dasatinib causes serious side effects, such as gastrointestinal bleeding and liver toxicity, possibly through the activation of ROCK kinase and MLC phosphorylation. At present, there is no effective prevention and treatment method. Previous research studies have shown that YQFM (YiQiFuMai powder injection) protects the blood-brain barrier by inhibiting the ROCK/MLC signaling pathway; whether YQFM can alleviate the side effects of dasatinib is unknown. In this study, dasatinib was injected (i.p. 70 mg/kg) and YQFM (i.p. 0.336 g/kg, 0.672 g/kg, 1.342 g/kg) was given in advance for 3 days to mice, to explore the effect of YQFM on side effects induced by Dasatinib. The results confirmed that YQFM significantly decreased Evans blue leakage in the small intestine and increased intestinal blood flow, increased the expression of ZO-1, Occludin, and VE-cadherin, and reduced the contents of D-lactic acid, s-VE-cadherin, Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) in serum. Finally, YQFM inhibited the expression of ROCK-1 and phosphorylation of MLC induced by Dasatinib. These findings suggested that YQFM could improve the side effects caused by Dasatinib linked with the ROCK/MLC signaling pathway, as shown in the graphical abstract.http://dx.doi.org/10.1155/2020/4646029 |