Dihydroartemisinin inhibits the tumorigenesis and invasion of gastric cancer by regulating STAT1/KDR/MMP9 and P53/BCL2L1/CASP3/7 pathways

小桶 双氢青蒿素 癌变 癌症研究 生物 细胞凋亡 癌症 基因 基因表达 转录组 免疫学 青蒿素 遗传学 恶性疟原虫 疟疾
作者
Rui Liang,Wei Chen,Xiaoyu Chen,Hui‐Ning Fan,Jing Zhang,Jingde Zhu
出处
期刊:Pathology Research and Practice [Elsevier BV]
卷期号:218: 153318-153318 被引量:19
标识
DOI:10.1016/j.prp.2020.153318
摘要

Dihydroartemisinin (DHA), an effective antimalarial drug, has been widely investigated as an anti-tumor agent. Although previous studies have indicated the potential therapeutic effects of DHA on multiple malignancies, its detailed molecular mechanisms in gastric cancer (GC) are still undocumented. In the present study, we applied network pharmacology and bioinformatics (gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses) to obtain the collective targets of DHA and GC and analyzed their involvement in constructing a protein-protein interaction (PPI) network. The top 10% hub targets in this network were identified, and TCGA database was utilized for the single gene analysis of their correlation with the prognosis of GC. CCK8, EdU, Transwell, and flow cytometry analyses were conducted, and subcutaneous xenograft tumor models were constructed to assess the effects of DHA on the tumorigenesis and invasion of GC. Furthermore, the targets of DHA were verified by molecular docking, quantitative real-time PCR (qPCR) and western blot analyses in GC cells. The results indicated that the common targets of DHA and GC were enriched in multiple cancer-related pathways including KDR, STAT1 and apoptosis signaling pathways, where the core genes included KDR, MMP9, STAT1, TP53, CASP3/7 and BCL2L1. The lowered expression of KDR and increased expression of TP53 and CASP7 harbored a favorable survival for patients with GC patients. CASP7 showed a positive correlation with CASP3 but a negative correlation with KDR and could be regarded as an independent protective factor for overall survival in GC. Moreover, DHA treatment induced cell apoptosis and suppressed the cell proliferation, DNA synthesis, cycle progression and invasive capabilities both in vitro and in vivo. DHA also upregulated p53, CASP3, and cleaved-CASP3 and downregulated BCL2L1, MMP9, KDR, p-KDR, STAT1 and p-STAT1 in GC cell lines. In conclusion, DHA could suppress the tumorigenesis and invasion of GC by regulating STAT1/KDR/MMP9 and p53/BCL2L1/CASP3/7 pathways. Our findings might provide a novel approach for the treatment of GC.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
刚刚
小超人完成签到,获得积分20
刚刚
LSY完成签到,获得积分10
1秒前
abby123完成签到,获得积分10
1秒前
1秒前
choi发布了新的文献求助10
1秒前
卓梨完成签到 ,获得积分10
2秒前
taco完成签到,获得积分10
2秒前
烟花应助zhangtengteng采纳,获得10
2秒前
妮妮完成签到,获得积分10
2秒前
sota完成签到,获得积分10
3秒前
含蓄心锁完成签到,获得积分10
3秒前
3秒前
3秒前
123完成签到,获得积分10
3秒前
科目三应助馨馨采纳,获得10
4秒前
科研通AI2S应助MosesXie采纳,获得10
4秒前
一点不懂发布了新的文献求助10
4秒前
和谐的寄凡完成签到,获得积分10
4秒前
5秒前
无奈敏完成签到,获得积分10
5秒前
5秒前
djbj2022发布了新的文献求助80
6秒前
6秒前
Isaac完成签到,获得积分10
6秒前
弥秋完成签到,获得积分10
7秒前
欣慰小丸子完成签到,获得积分10
7秒前
向日葵完成签到,获得积分10
7秒前
务实的鸽子完成签到,获得积分10
7秒前
leon发布了新的文献求助10
7秒前
仂尤发布了新的文献求助10
8秒前
zzcres完成签到,获得积分10
8秒前
小海完成签到,获得积分10
9秒前
万能图书馆应助choi采纳,获得10
9秒前
常若冰完成签到,获得积分10
9秒前
yyauthor完成签到,获得积分10
9秒前
secret完成签到,获得积分20
9秒前
9秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969060
求助须知:如何正确求助?哪些是违规求助? 3513962
关于积分的说明 11171223
捐赠科研通 3249302
什么是DOI,文献DOI怎么找? 1794772
邀请新用户注册赠送积分活动 875377
科研通“疑难数据库(出版商)”最低求助积分说明 804769