PMID- 35560016
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20220610
IS  - 2666-335X (Electronic)
IS  - 2666-335X (Linking)
VI  - 3
IP  - 2
DP  - 2022 May
TI  - Antitumor effect of the selective hypoxia-inducible factor-1 inhibitors 
      echinomycin and PX-478 on uterine fibroids.
PG  - 187-196
LID - S2666-335X(22)00005-2 [pii]
LID - 10.1016/j.xfss.2022.01.005 [doi]
AB  - OBJECTIVE: To investigate the antitumor effects of the selective 
      hypoxia-inducible factor-1 (HIF-1) inhibitors echinomycin and PX-478 on uterine 
      fibroids. DESIGN: Experimental study using in vitro primary culture systems and 
      an in vivo mouse xenograft model. SETTING: Academic university center. 
      PATIENT(S): Women with uterine fibroids who underwent hysterectomy or myomectomy. 
      INTERVENTION(S): Administration of the selective HIF-1 inhibitors echinomycin and 
      PX-478 to the media of the primary cultured uterine fibroid cells and to nonobese 
      diabetic/severe combined immunodeficient mice bearing fibroid xenografts 
      consisting of the primary cultured fibroid cells and type Ⅰ collagen gels beneath 
      the kidney capsule. MAIN OUTCOME MEASURE(S): Cell proliferation was measured by 
      Cell Counting Kit-8 assay. Apoptosis was evaluated by terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling assay and by measuring caspase 3 and 
      7 activities. The xenografts were evaluated by gross appearance, surface area, 
      and histology. The Ki-67 index was measured to evaluate proliferation of the 
      xenografts. RESULT(S): Both echinomycin and PX-478 inhibited cell proliferation 
      and induced apoptosis in fibroid cells cultured under hypoxia and normoxia. 
      Enlargement of the fibroid xenografts was significantly attenuated. The Ki-67 
      index significantly decreased after the administration of the HIF-1 inhibitors in 
      the xenograft model. Eight of 27 xenografts treated with the HIF-1 inhibitors 
      contained calcification and hyalinizing components from 3 days after the grafting 
      to 2 weeks, suggesting that the HIF-inhibitors induce degeneration of the fibroid 
      xenografts. CONCLUSION(S): The selective HIF-1 inhibitors echinomycin and PX-478 
      show antitumor effects against uterine fibroids both in vitro and in vivo. These 
      findings support the potential use of HIF-1 inhibitors for the treatment of 
      uterine fibroids.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Xu, Linlin
AU  - Xu L
AD  - Department of Reproductive Medicine, Graduate School of Medicine, Chiba 
      University, Chiba, Japan.
FAU - Ishikawa, Hiroshi
AU  - Ishikawa H
AD  - Department of Reproductive Medicine, Graduate School of Medicine, Chiba 
      University, Chiba, Japan. Electronic address: ishikawa@chiba-u.jp.
FAU - Zhou, Yanruo
AU  - Zhou Y
AD  - Department of Reproductive Medicine, Graduate School of Medicine, Chiba 
      University, Chiba, Japan.
FAU - Kobayashi, Tatsuya
AU  - Kobayashi T
AD  - Department of Reproductive Medicine, Graduate School of Medicine, Chiba 
      University, Chiba, Japan.
FAU - Shozu, Makio
AU  - Shozu M
AD  - Department of Reproductive Medicine, Graduate School of Medicine, Chiba 
      University, Chiba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220121
PL  - United States
TA  - F S Sci
JT  - F&S science
JID - 101765857
RN  - 0 (2-amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Mustard Compounds)
RN  - 0 (Phenylpropionates)
RN  - 512-64-1 (Echinomycin)
SB  - IM
MH  - Animals
MH  - *Echinomycin/pharmacology
MH  - Female
MH  - Humans
MH  - Hypoxia
MH  - Hypoxia-Inducible Factor 1
MH  - Ki-67 Antigen
MH  - *Leiomyoma/drug therapy
MH  - Mice
MH  - Mustard Compounds
MH  - Phenylpropionates
OTO - NOTNLM
OT  - Echinomycin
OT  - PX-478
OT  - hypoxia-inducible factor-1
OT  - uterine fibroids
OT  - xenograft model
EDAT- 2022/05/14 06:00
MHDA- 2022/05/18 06:00
CRDT- 2022/05/13 18:45
PHST- 2021/11/09 00:00 [received]
PHST- 2022/01/12 00:00 [revised]
PHST- 2022/01/14 00:00 [accepted]
PHST- 2022/05/13 18:45 [entrez]
PHST- 2022/05/14 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
AID - S2666-335X(22)00005-2 [pii]
AID - 10.1016/j.xfss.2022.01.005 [doi]
PST - ppublish
SO  - F S Sci. 2022 May;3(2):187-196. doi: 10.1016/j.xfss.2022.01.005. Epub 2022 Jan 
      21.