PMID- 32568828
OWN - NLM
STAT- MEDLINE
DCOM- 20210615
LR  - 20211204
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 31
IP  - 8
DP  - 2020 Sep
TI  - Cucurbitacin E inhibits esophageal carcinoma cell proliferation, migration, and 
      invasion by suppressing Rac1 expression through PI3K/AKT/mTOR pathway.
PG  - 847-855
LID - 10.1097/CAD.0000000000000961 [doi]
AB  - As an oxygenated tetracyclic triterpenoid, Cucurbitacin E (CuE) possesses 
      potential antitumor properties in sorts of malignancies. However, its effect on 
      human esophageal carcinoma cells has not been previously unearthed, and the 
      mechanism underlying its anticarcinoma activity remains vague. Hence, this study 
      was arranged to probe the function of CuE on esophageal carcinoma cells and its 
      specific mechanism. Human esophageal carcinoma cells (ECA109 and EC9706) and 
      human normal esophageal epithelial cells (Het-1A) were selected for subsequent 
      experiments. The expression levels of Rac1 in esophageal carcinoma cells were 
      measured. After transfection of sh-Rac1 or pCDNA3.1-Rac1, esophageal carcinoma 
      cells were exposed to CuE. Then, 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 
      5-ethynyl-2'-deoxyuridine staining were utilized for measurement of cell 
      proliferation ability, cell scratch assay for inspection of cell migration rate, 
      and Transwell for detection of cell invasion ability. The phosphorylation levels 
      of protein kinase B and mTOR were analyzed by Western blot. Rac1 was highly 
      expressed in esophageal carcinoma cells. Transfection of sh-Rac1 in esophageal 
      carcinoma cells resulted in suppression on cell proliferation, migration, and 
      invasion, as well as downregulated phosphorylation levels of AKT and mammalian 
      target of rapamycin (mTOR) in esophageal carcinoma cells, while transfection of 
      pCDNA3.1-Rac1 had an opposite effect, implicating that Rac1 can promote the 
      viability of esophageal carcinoma cells. Esophageal carcinoma cells subjected to 
      CuE treatment had decreased expression of Rac1, suppressed cell viability, and 
      decreased phosphorylation levels of AKT and mTOR. Transfection of pCDNA3.1-Rac1 
      and CuE treatment in esophageal carcinoma cells enhanced viability of esophageal 
      carcinoma cells and promoted the phosphorylation levels of AKT and mTOR in 
      comparison with cells treated with CuE alone. CuE inhibits proliferation, 
      invasion, and migration of esophageal carcinoma cells via downregulating Rac1 to 
      block the phosphoinositide 3-kinase/AKT/mTOR pathway.
FAU - Zhang, Luquan
AU  - Zhang L
AD  - Esophageal Mediastinal Division of Thoracic Surgery, Affiliated Tumor Hospital of 
      Harbin Medical University, Harbin, Heilongjiang, China.
FAU - Liang, Hao
AU  - Liang H
FAU - Xin, Yanzhong
AU  - Xin Y
LA  - eng
PT  - Journal Article
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RAC1 protein, human)
RN  - 0 (Triterpenes)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - V8A45XYI21 (cucurbitacin E)
SB  - IM
MH  - Apoptosis
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Cell Cycle
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Esophageal Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Esophageal Squamous Cell Carcinoma/drug therapy/genetics/metabolism/pathology
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Prognosis
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Triterpenes/*pharmacology
MH  - Tumor Cells, Cultured
MH  - rac1 GTP-Binding Protein/genetics/*metabolism
EDAT- 2020/06/23 06:00
MHDA- 2021/06/16 06:00
CRDT- 2020/06/23 06:00
PHST- 2020/06/23 06:00 [pubmed]
PHST- 2021/06/16 06:00 [medline]
PHST- 2020/06/23 06:00 [entrez]
AID - 00001813-202009000-00010 [pii]
AID - 10.1097/CAD.0000000000000961 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2020 Sep;31(8):847-855. doi: 10.1097/CAD.0000000000000961.