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dc.contributor.authorChintalaramulu, Naveen
dc.contributor.authorVadivelu, Raja
dc.contributor.authorNam-Trung, Nguyen
dc.contributor.authorCock, Ian Edwin
dc.date.accessioned2020-09-14T03:58:15Z
dc.date.available2020-09-14T03:58:15Z
dc.date.issued2020
dc.identifier.issn0925-4692
dc.identifier.doi10.1007/s10787-020-00711-9
dc.identifier.urihttp://hdl.handle.net/10072/397452
dc.description.abstractInflammatory 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofjournalInflammopharmacology
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode1115
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsImmunology
dc.subject.keywordsPharmacology & Pharmacy
dc.subject.keywordsToxicology
dc.titleLapatinib inhibits doxorubicin induced migration of HER2-positive breast cancer cells
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationChintalaramulu, N; Vadivelu, R; Nam-Trung, N; Cock, IE, Lapatinib inhibits doxorubicin induced migration of HER2-positive breast cancer cells, Inflammopharmacology, 2020
dcterms.dateAccepted2020-04-15
dc.date.updated2020-09-14T03:56:57Z
gro.description.notepublicThis publication has been entered in Griffith Research Online as an advanced online version.
gro.hasfulltextNo Full Text
gro.griffith.authorCock, Ian E.
gro.griffith.authorNguyen, Nam-Trung
gro.griffith.authorVadivelu, Raja


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