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Modified Shenlingbaizhu Decoction represses the pluripotency of colorectal cancer stem cells by inhibiting TGF-β mediated EMT program.

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作者：
Dai Yu[1] * ; Wang Hao[1] * ; Sun Ruibo[1] ; Diao Jianxin[1] ; Ma Ye[1] ; Shao Meng[1] ; Xu Yihua[1] ; Zhang Qingyuan[1] ; Gao Zhuowei[1,2] ; Zeng Zhiyun[1] ; Zhang Lihua[3] ; Sun Xuegang[1,4,*1] ;
机构： [1]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China [2]Shunde Hospital, Guangzhou University of Chinese Medicine, Foshan, 528333, Guangdong, China [3]Traditional Chinese Medicine Integrated Hospital, Southern Medical University, Guangzhou, 510315, Guangdong, China [4]Department of traditional Chinese medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, 510260, Guangdong, China
出处：
DOI： 10.1016/j.phymed.2022.154234
ISSN：

关键词： Modified Shenlingbaizhu decoction Colorectal cancer Colorectal cancer stem cells Epithelial-mesenchymal transition TGF-β/Smad signaling pathway

摘要：
The Modified Shenlingbaizhu Decoction (MSD) utilizes various phytomedicines has been applied to treat colorectal cancer (CRC). Colorectal cancer stem cells (CSCs) have proven to be tightly associated with CRC progression and metastasis. The mechanism of MSD's inhibitory effect on CSCs has not been determined.To figure out how MSD inhibits the pluripotency of CSCs and impedes the EMT program.The ingredients of MSD extracts were characterized by high-performance liquid chromatography (HPLC). BALB/c-nu mice were transplanted into EGFP labeled SW480 CRC cells and the tumor weight and volume were recorded before and after various doses of MSD treatment. The concentration of TGF-β1 was quantified with an Enzyme-linked immunosorbent assay. To delineate the logical relationship between EMT and CSCs regulated by MSD, TGF-β/Smad inhibitor and activator were adopted in tumor-bearing mice and diverse CRC cell lines. Cancer stem cell markers were analyzed by flow cytometry. In vitro analysis of cell motility and viability were done using CCK-8, wound healing, and invasion assay. Immunohistochemistry (IHC) and western blotting (WB) were used for detecting protein expression. The collected results were statistically analyzed with GraphPad Prism 8.0.MSD treatment significantly reduced the size of colorectal cancer tumors and lowered the serum content of TGF-β1 in mice. Importantly, MSD markedly reduced the expression of pluripotent factors and depressed CD133+ stem cells in the tumor tissues. The TGF-β/Smad inhibitor neutralized the EMT signaling and lowered the pluripotency by dephosphorylation of SMAD2/3. Similarly, MSD attenuated the pluripotency by limiting TGF-β/Smad signaling-induced EMT in vivo. MSD inhibited colorectal cancer cell proliferation, migration, and invasion.MSD inhibits the growth of colorectal cancer. It dampens the pluripotency of CSCs by repressing the TGF-β-induced EMT program.Copyright © 2022. Published by Elsevier GmbH.

基金：
This work was supported by the National Science Foundation of China (81974554, 81774172, 81904075), Key-Area Research and Development Program of Guangdong Province, Modernization of Chinese medicine in Lingnan (2020B1111100011), Planned Science Technology Project of Guangzhou (202002030111), Guangdong Natural Science Foundation (2020A1515010229), Guangdong Province Bureau of Traditional Chinese Medicine Scientific Research Project (20184016), College Students’ innovation and Entrepreneurship Project of Southern medical University (S201912121184).
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外文
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出版当年[2021]版：
大类 | 2 区 医学
小类 | 1 区 植物科学 1 区 全科医学与补充医学 1 区 药学 2 区 药物化学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 药物化学 1 区 全科医学与补充医学 1 区 药学 1 区 植物科学
JCR分区：
出版当年[2020]版：
Q1 PHARMACOLOGY & PHARMACY Q1 PLANT SCIENCES Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 CHEMISTRY, MEDICINAL
最新[2023]版：
Q1 CHEMISTRY, MEDICINAL Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 PHARMACOLOGY & PHARMACY Q1 PLANT SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China
共同第一作者：
通讯作者：
通讯机构： [1]The Key Laboratory of Molecular Biology, State Administration of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China [4]Department of traditional Chinese medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, 510260, Guangdong, China [*1]The Key Laboratory of Molecular Biology, State Administration of Traditional Chi, School of Traditional Chinese Medicine, Southern Medical University, No. 1838, guang zhou da dao bei, sc, Guangzhou 510515, China.
推荐引用方式(GB/T 7714)：
Dai Yu,Wang Hao,Sun Ruibo,et al.Modified Shenlingbaizhu Decoction represses the pluripotency of colorectal cancer stem cells by inhibiting TGF-β mediated EMT program.[J].PHYTOMEDICINE.2022,103:doi:10.1016/j.phymed.2022.154234.
APA：
Dai Yu,Wang Hao,Sun Ruibo,Diao Jianxin,Ma Ye...&Sun Xuegang.(2022).Modified Shenlingbaizhu Decoction represses the pluripotency of colorectal cancer stem cells by inhibiting TGF-β mediated EMT program..PHYTOMEDICINE,103,
MLA：
Dai Yu,et al."Modified Shenlingbaizhu Decoction represses the pluripotency of colorectal cancer stem cells by inhibiting TGF-β mediated EMT program.".PHYTOMEDICINE 103.(2022)

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