Cytotoxic Effects of the Dual ErbB Tyrosine Kinase Inhibitor, Lapatinib, on Walker 256 Rat Breast Tumour and IEC-6 Rat Normal Small Intestinal Cell Lines.

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dc.contributor.authorWan Mohamad Zain, W.N.I.Z.
dc.contributor.authorBowen, J.
dc.contributor.authorBateman, E.
dc.contributor.authorKeefe, D.
dc.date.issued2020
dc.description.abstractLapatinib is an orally administered, dual ErbB1/ErbB2 tyrosine kinase inhibitor (TKI). It is effective in ErbB2 + ve breast cancer treatment. However, lapatinib is associated with diarrhoea with an incidence of 47–75%. The mechanism of ErbB1 TKI-induced diarrhoea remains unclear. ErbB1 or epidermal growth factor receptor (EGFR) is expressed in gastrointestinal mucosa whereby the primary site for drug absorption is intestine. Thus, administration of ErbB1 oral TKI may disrupt gut homeostasis, leading to diarrhoea. Nevertheless, further investigations are required. We observed that lapatinib inhibited 50% Walker 256 breast tumour cells and IEC-6 small intestinal cell growth. Higher percentage of necrosis was observed in lapatinib-treated Walker 256. Lapatinib-treated IEC-6 showed higher percentage of late apoptosis. Only ErbB2 mRNA was detected in Walker 256 but both ErbB1 and ErbB2 mRNAs were detected in IEC-6, yet both protein staining were detected in both cells. Lapatinib exhibited cytotoxic properties on ErbB1/ErbB2 expressing cell lines, with intestinal cells being more sensitive to lapatinib compared to tumour cells. Lapatinib induced necrosis in tumour cells, while inducing late apoptosis in intestinal cells may explain lapatinib-induced diarrhoea in patients administered with the drug which could be due to apoptosis of intestinal epithelial cells leading to barrier disruption and consequently diarrhoea.
dc.description.statementofresponsibilityWan Nor I'zzahWan Mohamad Zain, Joanne Bowen, Emma Bateman, and Dorothy Keefe
dc.identifier.citationBiomedicines, 2020; 8(1):2-1-2-14
dc.identifier.doi10.3390/biomedicines8010002
dc.identifier.issn2227-9059
dc.identifier.issn2227-9059
dc.identifier.orcidBowen, J. [0000-0003-0876-0031]
dc.identifier.orcidBateman, E. [0000-0003-1665-102X]
dc.identifier.orcidKeefe, D. [0000-0001-9377-431X]
dc.identifier.urihttps://hdl.handle.net/2440/145775
dc.language.isoen
dc.publisherMDPI AG
dc.rights© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.source.urihttps://doi.org/10.3390/biomedicines8010002
dc.subjectlapatinib; ErbB1/ErbB2 TKI; Walker 256; IEC-6; diarrhoea
dc.titleCytotoxic Effects of the Dual ErbB Tyrosine Kinase Inhibitor, Lapatinib, on Walker 256 Rat Breast Tumour and IEC-6 Rat Normal Small Intestinal Cell Lines.
dc.typeJournal article
pubs.publication-statusPublished

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