PMID- 31092430
OWN - NLM
STAT- MEDLINE
DCOM- 20190523
LR  - 20190523
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 39
IP  - 5
DP  - 2019 May
TI  - Lapatinib Inhibits Amphiregulin-induced BeWo Choriocarcinoma Cell Proliferation 
      by Reducing ERK1/2 and AKT Signaling Pathways.
PG  - 2377-2383
LID - 10.21873/anticanres.13355 [doi]
AB  - BACKGROUND: Human choriocarcinoma is the most aggressive type of gestational 
      trophoblastic neoplasia. The expression of epidermal growth factor receptor 
      (EGFR) in choriocarcinomas is significantly higher than those of trophoblastic 
      cells in healthy placentas. Lapatinib is a potent EGFR and human epidermal growth 
      factor receptor 2 (HER2) inhibitor that inhibits cell proliferation and induces 
      apoptosis in various human cancer cells. Amphiregulin (AREG) is the most abundant 
      EGFR ligand in amniotic fluid during human pregnancy. AIM: To explore the role of 
      AREG in human choriocarcinoma cell proliferation. MATERIALS AND METHODS: The 
      effect of lapatinib and AREG on cell proliferation was examined by the MTT assay. 
      Western blots were used to investigate EGFR and HER2 expression, and the 
      activation of caspase-3, extracellular signal-regulated kinases 1/2 (ERK1/2) and 
      phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) signaling pathways. 
      RESULTS: Treatment with lapatinib reduced BeWo cell proliferation by inducing 
      apoptosis. Moreover, AREG treatment stimulated BeWo cell proliferation by 
      activating ERK1/2 and PI3K/AKT signaling pathways, which was blocked by 
      lapatinib. CONCLUSION: Targeting EGFR/HER2 might be a useful therapeutic strategy 
      for human choriocarcinoma.
CI  - Copyright(c) 2019, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Pires, Leticia Vicosa
AU  - Pires LV
AD  - Department of Gynaecology and Obstetrics, Porto Alegre Clinical Hospital, Porto 
      Alegre, RS, Brazil.
AD  - Department of Obstetrics and Gynaecology, BC Children's Hospital Research 
      Institute, University of British Columbia, Vancouver, BC, Canada.
FAU - Yi, Yuyin
AU  - Yi Y
AD  - Department of Obstetrics and Gynaecology, BC Children's Hospital Research 
      Institute, University of British Columbia, Vancouver, BC, Canada.
FAU - Cheng, Jung-Chien
AU  - Cheng JC
AD  - Department of Obstetrics and Gynaecology, BC Children's Hospital Research 
      Institute, University of British Columbia, Vancouver, BC, Canada.
FAU - Pizzolato, Lolita Schneider
AU  - Pizzolato LS
AD  - Department of Physiology, Basic Health Science Institute, Federal University of 
      Rio Grande do Sul, Porto Alegre, RS, Brazil.
FAU - Cordero, Elvira
AU  - Cordero E
AD  - Department of Physiology, Basic Health Science Institute, Federal University of 
      Rio Grande do Sul, Porto Alegre, RS, Brazil.
FAU - Leung, Peter C K
AU  - Leung PCK
AD  - Department of Obstetrics and Gynaecology, BC Children's Hospital Research 
      Institute, University of British Columbia, Vancouver, BC, Canada 
      peter.leung@ubc.ca.
FAU - Brum, Ilma Simoni
AU  - Brum IS
AD  - Department of Gynaecology and Obstetrics, Porto Alegre Clinical Hospital, Porto 
      Alegre, RS, Brazil.
AD  - Department of Physiology, Basic Health Science Institute, Federal University of 
      Rio Grande do Sul, Porto Alegre, RS, Brazil.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Amphiregulin)
RN  - 0VUA21238F (Lapatinib)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
SB  - IM
MH  - Amphiregulin/*genetics/pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Choriocarcinoma/drug therapy/*genetics/pathology
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Lapatinib/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Oncogene Protein v-akt/genetics
MH  - Receptor, ErbB-2/antagonists & inhibitors/*genetics
OTO - NOTNLM
OT  - EGFR
OT  - HER2
OT  - Lapatinib
OT  - choriocarcinoma
EDAT- 2019/05/17 06:00
MHDA- 2019/05/24 06:00
CRDT- 2019/05/17 06:00
PHST- 2019/01/31 00:00 [received]
PHST- 2019/04/10 00:00 [revised]
PHST- 2019/04/11 00:00 [accepted]
PHST- 2019/05/17 06:00 [entrez]
PHST- 2019/05/17 06:00 [pubmed]
PHST- 2019/05/24 06:00 [medline]
AID - 39/5/2377 [pii]
AID - 10.21873/anticanres.13355 [doi]
PST - ppublish
SO  - Anticancer Res. 2019 May;39(5):2377-2383. doi: 10.21873/anticanres.13355.