RLIP inhibition suppresses breast-to-lung metastasis.
ATP-Binding Cassette Transporters
/ antagonists & inhibitors
Animals
Breast
/ drug effects
Breast Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Survival
/ drug effects
Female
Flavanones
/ pharmacology
GTPase-Activating Proteins
/ antagonists & inhibitors
Humans
Lung
/ pathology
Lung Neoplasms
/ drug therapy
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Metastasis
/ drug therapy
Xenograft Model Antitumor Assays
/ methods
Breast cancer
Chemotherapeutics
Lung
Metastasis
Phytochemicals
RLIP
Journal
Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053
Informations de publication
Date de publication:
10 04 2019
10 04 2019
Historique:
received:
17
10
2018
revised:
08
01
2019
accepted:
19
01
2019
pubmed:
27
1
2019
medline:
18
12
2019
entrez:
27
1
2019
Statut:
ppublish
Résumé
Breast tumor metastasis is a leading cause of cancer-related deaths worldwide. Breast cancer (BC) cells frequently metastasize to the lungs, where they pose a formidable therapeutic challenge. In the current study, we evaluated the anti-proliferative and anti-metastatic effects of 2'-hydroxyflavanone (2HF) and RLIP inhibition in an array of triple-negative BC cell lines and an orthotopic mouse model of breast-to-lung metastasis. Compared to control treatment, RLIP inhibition reduced in-vitro cell viability and suppressed the migratory and invasive potential of BC cells. In-vitro studies showed that 2HF treatment reduced the expression of RLIP, KRAS, pERK, pSTAT3, and pP70S6K. Further, mice orthotopically implanted with lung-seeking luciferase-expressing TMD231 cells were treated with 2HF (50 mg/kg, b.w.), RLIP antisense (RAS; 5 mg/kg, b.w.), RLIP antibody (Rab; 5 mg/kg, b.w.) or a combination of 2HF + RAS + Rab. 2HF-, RAS-, and Rab-treated mice exhibited significantly lower primary tumor weight and reduced lung metastasis compared to control mice. Mice treated with a combination of 2HF + RAS + Rab exhibited no metastasis and significantly lower tumor weight than the single agent-treated mice. Collectively, our results suggest that 2HF has potential to be combined with RLIP inhibition/depletion to more effectively suppress primary breast tumor growth and metastasis to the lungs.
Identifiants
pubmed: 30684594
pii: S0304-3835(19)30043-6
doi: 10.1016/j.canlet.2019.01.023
pmc: PMC8806386
mid: NIHMS1772528
pii:
doi:
Substances chimiques
2'-hydroxyflavanone
0
ATP-Binding Cassette Transporters
0
Flavanones
0
GTPase-Activating Proteins
0
RALBP1 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
24-32Subventions
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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