Lapatinib inhibits doxorubicin induced migration of HER2-positive breast cancer cells.
Antineoplastic Agents
/ administration & dosage
Breast Neoplasms
/ drug therapy
Cell Line
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Survival
/ drug effects
Doxorubicin
/ administration & dosage
ErbB Receptors
/ antagonists & inhibitors
Female
Fibroblasts
/ drug effects
Humans
Lapatinib
/ administration & dosage
Protein Kinase Inhibitors
/ administration & dosage
Receptor, ErbB-2
/ antagonists & inhibitors
Triple Negative Breast Neoplasms
/ drug therapy
Cancer
Cytoskeleton
Doxorubicin
Lapatinib
Metastasis
Therapy
Journal
Inflammopharmacology
ISSN: 1568-5608
Titre abrégé: Inflammopharmacology
Pays: Switzerland
ID NLM: 9112626
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
28
01
2020
accepted:
15
04
2020
pubmed:
8
5
2020
medline:
2
7
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
Inflammatory breast cancer (IBC) is an uncommon and highly aggressive form of breast cancer. The disease is characterized by rapid progression with approximately 50% of IBC patients to have human epidermal growth factor receptor 2 (HER2) amplification. HER2-positive IBC is associated with unfavourable prognosis and increased risk of brain metastasis. Ironically, HER2-positive metastatic breast cancer is still prevalent where therapeutic targeting of HER2-receptor is well developed. In addition, the ability to accurately predict the risk of metastatic potential in these cells poses a substantial challenge. Lapatinib (Lap), a dual kinase inhibitor of HER2 and epidermal growth factor receptor is used in the treatment of advanced HER-2 positive breast cancers and is currently being evaluated in the adjuvant setting. In this study, we report the effectiveness of Lap in the suppression of low-dose response to doxorubicin (Dox) in HER2-positive SKBR3 cells. Upon treatment of SKBR3 cells with 0.1 µM of Dox, the cell viability was significantly increased as compared to the human mammary fibroblasts, and triple-negative human breast cancer MDA-MB-231 cells. Interestingly, the effect of 0.1 µM Dox revealed morphological changes consistent with a significant increase in the formation of prominent F-actin filaments and mitochondrial spread compared with the control SKBR3 cells. Furthermore, an enhanced migration was also evident in these cells. However, a combinational dose of 0.1 µM Dox + 5 µM Lap suppressed the observed phenotypic changes in the 0.1 µM Dox treated SKBR3 cells. There was a significant difference in the prominent F-actin filaments and the mitochondrial spread compared with the 0.1 µM Dox versus combination regimen of 0.1 µM Dox + 5 µM Lap. In addition, the combinational therapy showed a decrease in the percentage of wound closure when compared to the control. Hence, the combinational therapy in which Lap suppresses the low-dose effect of Dox in SKBR3 cells may provide an effective intervention strategy for reducing the risk of metastasis in HER2-positive breast cancers.
Identifiants
pubmed: 32378049
doi: 10.1007/s10787-020-00711-9
pii: 10.1007/s10787-020-00711-9
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Kinase Inhibitors
0
Lapatinib
0VUA21238F
Doxorubicin
80168379AG
EGFR protein, human
EC 2.7.10.1
ERBB2 protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1375-1386Références
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