题名 | Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway |
作者 | |
发表日期 | 2021-02 |
发表期刊 | Chinese Journal of Natural Medicines 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Article |
关键词 | Jiedu Sangen decoction 5-Fluorouracil resistance Glycolysis Apoptosis Colorectal cancer |
其他关键词 | DRUG-RESISTANCE ; HIF-1-ALPHA ; HYPOXIA ; APOPTOSIS ; PI3K/AKT ; CHEMOTHERAPY ; METABOLISM |
摘要 | Drug resistance is a major obstacle in the development of effective colorectal cancer(CRC) therapy. Our study aimed to explore the reversal abilities of Jiedu Sangen decoction(JSD) on the 5-fluorouracil(5-FU) resistance and its underlying molecular mechanisms. Expression changes in HIF-1 of CRC tissues were firstly revealed by bioinformatics analysis. Afterwards, cell viabilities of JSD and 5-FU treatments on 5-FU resistant human colon cancer cells(HCT-8/5-FU) were determined. Expressions of phosphoinositide 3-kinase(PI3 K), protein kinase B(AKT)/p-AKT, hypoxia-inducible factor 1(HIF-1α), as well as glycolysis related proteins such as L-lactate dehydrogenase A(LDHA), Glucose transporter type 1(Glut1), Hexokinase 2(HKII), and cysteinyl aspartate specific proteinase(Caspase) family members in HCT-8/5-FU cells, HIF-1α silenced HCT-8/5-FU cells and tumor tissues were detected by western blotting. HIF-1α was found over expressed in CRC tissues according to public available datasets in Oncomine. Growth inhibition rates of HCT-8/5-FU cells were increased along with the increase of JSD concentrations. JSD caused down-regulated HIF-1α, PI3 K,AKT/p-AKT, HKII and Glut1, as well as up-regulated Caspase3 and Caspase9 in HCT-8/5-FU cells and tumor tissues. In HIF-1α silenced HCT-8/5-FU cells, synergistic group showed significantly reduced expression levels of PI3 K, AKT, p-AKT. Additionally, upregulated expressions of Caspase6 and Caspase7 were observed. JSD combined with 5-FU also exhibited obvious inhibitory efficiency on tumor growth in vivo. JSD may reverse 5-FU resistance by suppressing glycolysis via PI3 K/AKT/HIF-1α signaling pathway,thereby inhibiting glycolysis and induce apoptosis to enhance anti-tumor activity. |
资助项目 | supported by General Research Program for Education of Zhejiang Provincial (No. Y202045212);; the Seventh Batch of Provincial Famous Traditional Chinese Medicine Studios in Zhejiang Province;; Cultivation Program for Innovative Talent Graduate Students (No. 721100G00713);; Zhejiang Provincial Program for the Cultivation of the Young and Middle-Aged Academic Leaders in Colleges and Universities (No. 2017-248);; Zhejiang Provincial Project for the Key Discipline of Traditional Chinese Medicine (No. 2017-XK-A09);; Zhejiang Provincial Project for the Science and Technology Program of Traditional Chinese Medicine (No. 2015ZZ013) |
出版者 | CHINESE JOURNAL NATURAL MEDICINES |
出版地 | NANJING |
ISSN | 2095-6975 |
EISSN | 1875-5364 |
卷号 | 19期号:02页码:143-152 |
DOI | 10.1016/S1875-5364(21)60015-8 |
页数 | 10 |
WOS类目 | Integrative & Complementary Medicine ; Pharmacology & Pharmacy |
WOS研究方向 | Integrative & Complementary Medicine ; Pharmacology & Pharmacy |
WOS记录号 | WOS:000623397400007 |
收录类别 | CNKI ; SCOPUS ; SCIE ; PUBMED ; CSCD |
学科领域 | 医药、卫生 ; 药学 |
URL | 查看原文 |
CSCD记录号 | CSCD:6916508 |
PubMed ID | 33641785 |
SCOPUSEID | 2-s2.0-85101616260 |
通讯作者地址 | [SHEN, Min-He]Department of Medical Oncology,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,310006,China |
Scopus学科分类 | Drug Discovery;Complementary and Alternative Medicine |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/134203 |
专题 | 附属第一医院_中医科 |
通讯作者 | SHEN, Min-He |
作者单位 | 1.Department of Medical Oncology,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,310006,China; 2.The First Clinical Medical College of Zhejiang Chinese Medical University,Hangzhou,310053,China; 3.Department of Traditional Chinese Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China |
推荐引用方式 GB/T 7714 | SUN, Lei-Tao,ZHANG, Le-Yin,SHAN, Fei-Yu,et al. Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway[J]. Chinese Journal of Natural Medicines,2021,19(02):143-152. |
APA | SUN, Lei-Tao, ZHANG, Le-Yin, SHAN, Fei-Yu, SHEN, Min-He, & RUAN, Shan-Ming. (2021). Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway. Chinese Journal of Natural Medicines, 19(02), 143-152. |
MLA | SUN, Lei-Tao,et al."Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway".Chinese Journal of Natural Medicines 19.02(2021):143-152. |
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