Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis

Wenli Qiu,1 Zhongqiu Wang,1 Rong Chen,2 Haibo Shi,3 Yanxia Ma,4 Hongli Zhou,5 Muhan Li,4 Wenting Li,4 Haibin Chen,6 Hongguang Zhou7 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 2Department of Diagnostic Radiology and Nu...

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Main Authors: Qiu W, Wang Z, Chen R, Shi H, Ma Y, Zhou H, Li M, Li W, Chen H
Format: Article
Language:English
Published: Dove Medical Press 2020-11-01
Series:Cancer Management and Research
Subjects:
Online Access:https://www.dovepress.com/xiaoai-jiedu-recipe-suppresses-hepatocellular-carcinogenesis-through-t-peer-reviewed-article-CMAR
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author Qiu W
Wang Z
Chen R
Shi H
Ma Y
Zhou H
Li M
Li W
Chen H
Zhou H
author_facet Qiu W
Wang Z
Chen R
Shi H
Ma Y
Zhou H
Li M
Li W
Chen H
Zhou H
author_sort Qiu W
collection DOAJ
description Wenli Qiu,1 Zhongqiu Wang,1 Rong Chen,2 Haibo Shi,3 Yanxia Ma,4 Hongli Zhou,5 Muhan Li,4 Wenting Li,4 Haibin Chen,6 Hongguang Zhou7 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 2Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; 3Department of Oncology, Wuxi Xishan Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, Republic of China; 4Institute of Oncology, The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 5The First Clinical Medical College, Liaoning University of Chinese Medicine, Shenyang, Liaoning, Republic of China; 6Science and Technology Department, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 7Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of ChinaCorrespondence: Hongguang ZhouDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, Mainland ChinaTel +86 25 8861 8472Fax +86 25 8661 8139Email zhouhongguang2002@163.comPurpose: Xiaoai Jiedu recipe (XJR), a formula long used by Chinese National Medical Professor Zhou Zhongying, has potent antitumor properties, but the molecular mechanism is still unclear. The aim of the study was to investigate the antitumor mechanism of XJR on hepatocellular carcinoma (HCC) by focusing on miRNA.Methods: Three concentrations of XJR (low, middle, and high) were used to treat tumor xenograft mice models. Microarray technology was used to identify the differential expressed genes after XJR treatment, and bioinformatic tools and luciferase reporter assay to predict the potential pathways. HepG2 cells were transfected with inhibitor of miR-200b-3p to detect the effect of miR-200b-3p and Notch1 on tumor growth.Results: XJR effectively exerted anti-HCC effect both in vitro and in vivo. MiRNA chip analysis results showed that the expression of 75 miRNAs was upregulated and 158 miRNAs was downregulated in blood from XJR-treated mice. Further validation by using real-time polymerase chain reaction (RT-PCR) assay showed that the expression of five miRNAs (miR-453, miR-200b-3p, miR-135a-1-3p, miR-1960, miR-378a-5p, and miR-466f) was consistent with the results of miRNA chip analysis. Among them, miR-200b-3p was selected as candidate for further research. Results of the MTT, migration, and wound healing assays showed that down-expression of miR-200b-3p abrogated the effect of XJR on cell growth and metastasis. Luciferase reporter assay confirmed that Notch1 was the direct target of miR-200b-3p. XJR significantly decreased Notch1 expression in HepG2 cells, whereas miR-200B-3p inhibitor abrogated the XJR-induced decrease in Notch1 expression.Conclusion: This study indicated that XJR could effectively inhibit HCC and might exert its antitumor effect through the miR‐200b-3p/Notch1 axis. These findings provided new avenues for the use of XJR for prevention and treatment of HCC.Keywords: Xiaoai Jiedu recipe, hepatocellular carcinoma, miR‐200b-3p, Notch1
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spelling doaj.art-ba43f9aba0fa494a93bd4f4cccc80dfa2022-12-21T22:05:33ZengDove Medical PressCancer Management and Research1179-13222020-11-01Volume 12111211113158787Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axisQiu WWang ZChen RShi HMa YZhou HLi MLi WChen HZhou HWenli Qiu,1 Zhongqiu Wang,1 Rong Chen,2 Haibo Shi,3 Yanxia Ma,4 Hongli Zhou,5 Muhan Li,4 Wenting Li,4 Haibin Chen,6 Hongguang Zhou7 1Department of Radiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 2Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA; 3Department of Oncology, Wuxi Xishan Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, Republic of China; 4Institute of Oncology, The First Clinical Medical College, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 5The First Clinical Medical College, Liaoning University of Chinese Medicine, Shenyang, Liaoning, Republic of China; 6Science and Technology Department, Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of China; 7Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, Republic of ChinaCorrespondence: Hongguang ZhouDepartment of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, Mainland ChinaTel +86 25 8861 8472Fax +86 25 8661 8139Email zhouhongguang2002@163.comPurpose: Xiaoai Jiedu recipe (XJR), a formula long used by Chinese National Medical Professor Zhou Zhongying, has potent antitumor properties, but the molecular mechanism is still unclear. The aim of the study was to investigate the antitumor mechanism of XJR on hepatocellular carcinoma (HCC) by focusing on miRNA.Methods: Three concentrations of XJR (low, middle, and high) were used to treat tumor xenograft mice models. Microarray technology was used to identify the differential expressed genes after XJR treatment, and bioinformatic tools and luciferase reporter assay to predict the potential pathways. HepG2 cells were transfected with inhibitor of miR-200b-3p to detect the effect of miR-200b-3p and Notch1 on tumor growth.Results: XJR effectively exerted anti-HCC effect both in vitro and in vivo. MiRNA chip analysis results showed that the expression of 75 miRNAs was upregulated and 158 miRNAs was downregulated in blood from XJR-treated mice. Further validation by using real-time polymerase chain reaction (RT-PCR) assay showed that the expression of five miRNAs (miR-453, miR-200b-3p, miR-135a-1-3p, miR-1960, miR-378a-5p, and miR-466f) was consistent with the results of miRNA chip analysis. Among them, miR-200b-3p was selected as candidate for further research. Results of the MTT, migration, and wound healing assays showed that down-expression of miR-200b-3p abrogated the effect of XJR on cell growth and metastasis. Luciferase reporter assay confirmed that Notch1 was the direct target of miR-200b-3p. XJR significantly decreased Notch1 expression in HepG2 cells, whereas miR-200B-3p inhibitor abrogated the XJR-induced decrease in Notch1 expression.Conclusion: This study indicated that XJR could effectively inhibit HCC and might exert its antitumor effect through the miR‐200b-3p/Notch1 axis. These findings provided new avenues for the use of XJR for prevention and treatment of HCC.Keywords: Xiaoai Jiedu recipe, hepatocellular carcinoma, miR‐200b-3p, Notch1https://www.dovepress.com/xiaoai-jiedu-recipe-suppresses-hepatocellular-carcinogenesis-through-t-peer-reviewed-article-CMARxiaoai jiedu recipehepatocellular carcinomamir‐200b-3pnotch1
spellingShingle Qiu W
Wang Z
Chen R
Shi H
Ma Y
Zhou H
Li M
Li W
Chen H
Zhou H
Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis
Cancer Management and Research
xiaoai jiedu recipe
hepatocellular carcinoma
mir‐200b-3p
notch1
title Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis
title_full Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis
title_fullStr Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis
title_full_unstemmed Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis
title_short Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p /Notch1 axis
title_sort xiaoai jiedu recipe suppresses hepatocellular carcinogenesis through the mir 200b 3p notch1 axis
topic xiaoai jiedu recipe
hepatocellular carcinoma
mir‐200b-3p
notch1
url https://www.dovepress.com/xiaoai-jiedu-recipe-suppresses-hepatocellular-carcinogenesis-through-t-peer-reviewed-article-CMAR
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