Oncotarget

Research Papers:

Synergistic antitumor activity by combining trastuzumab with retinoic acid in HER2 positive human breast cancer cells

Fiorella Vanderhoeven, Analía Lourdes Redondo, Ana Laura Martinez, Laura María Vargas-Roig, Angel Matias Sanchez and Marina Inés Flamini _

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Oncotarget. 2018; 9:26527-26542. https://doi.org/10.18632/oncotarget.25480

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Abstract

Fiorella Vanderhoeven1, Analía Lourdes Redondo1, Ana Laura Martinez1, Laura María Vargas-Roig1,2, Angel Matias Sanchez1 and Marina Inés Flamini1

1Instituto de Medicina y Biología Experimental de Cuyo, Centro Científico Tecnológico, Mendoza, Argentina

2Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina

Correspondence to:

Marina Inés Flamini, email: mflamini@mendoza-conicet.gob.ar

Keywords: anti-ErbB2 therapies; Moesin; focal adhesion kinase; adhesion; migration

Received: February 01, 2018    Accepted: May 08, 2018    Published: May 29, 2018

ABSTRACT

Breast cancer can be classified into molecular subtypes. Tumors overexpressing HER2 protein are more aggressive and metastatic; hence, patients have a poor prognosis. Anti-HER2 strategies, such as the monoclonal antibody Trastuzumab (Tz), have therefore been developed. Despite this progress, not all patients respond to the treatment. Retinoic acid (RA) has been proposed as an adjuvant treatment of breast carcinoma because of its ability to inhibit cell growth. We evaluated the effect of Tz in combination with RA on the viability, adhesion, migration, invasion and expression of migration-related proteins in SKBR3 and BT-474 human breast cancer cells. MTT, pharmacological interaction analysis, immunofluorescence, adhesion/migration/invasion and Western blot assays were performed. The coadministration of both drugs synergistically decreased cell survival. Tz+RA significantly decreased adhesion/migration/invasion in both cell types. Tz+RA strongly reduced FAK and HER2 expression and induced nuclear FAK translocation. In addition, a granular distribution of HER2 receptor was observed after the combined treatment. In conclusion, the coadministration of both drugs in patients with this type of cancer could contribute to the improvement of their prognosis and reduce the adverse effects of therapy because the applied Tz doses would be lower due to the adjuvant effect of RA.


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