Advances in Clinical and Experimental Medicine

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 2, February, p. 151–157

doi: 10.17219/acem/89770

Publication type: original article

Language: English

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Creative Commons BY-NC-ND 3.0 Open Access

Anti-neoplastic effects of aprotinin on human breast cancer cell lines: In vitro study

Saeed Soleyman-Jahi1,2,3,A,B,C,D,E,F, Fatemeh Sadeghi1,2,B,C,D,E,F, Ziba Afshari1,A,B,E,F, Tahereh Barati4,B,E,F, Sevil Ghasemi1,A,D,E,F, Samad Muhammadnejad5,A,C,E,F, Saeid Amanpour4,A,E,F, Kazem Zendehdel1,A,C,E,F

1 Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Iran

2 Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran

3 Division of Gastroentrology, Department of Internal Medicine, Washington University, St Louis, USA

4 Cancer Models Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Iran

5 Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Iran

Abstract

Background. Aprotinin is a nonspecific serine protease inhibitor, which can inhibit plasminogen-plasmin system and matrix metalloproteinases. Aprotinin has been investigated as an antitumor agent. However, its antineoplastic effects on breast cancer (BC) have not been investigated yet.
Objectives. The objective of this study was to assess the inhibitory effects of aprotinin on human BC cell lines. We assessed the effects of aprotinin on local invasion and survival of human BC cell lines MDA-MB-231, SK-BR-3 and MCF-7 in vitro.
Material and Methods. CHEMICON cell invasion assay kit was used to assess local invasion, and (3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay was used to determine the antiproliferative activity of aprotinin. Human dermal fibroblast (HDF-1) cell line was used as control normal cells.
Results. Cancer cell lines showed more invasion characteristics compared to HDF-1. Aprotinin significantly decreased the invasiveness of MDA-MB-231 in concentrations of 1 trypsin inhibitor unit (TIU)/mL, 1.3 TIU/mL and 1.7 TIU/mL in comparison with the untreated group (analysis of variance (ANOVA) p < 0.001). Treatment of SK-BR-3 with 1.3 TIU/mL aprotinin caused no significant reduction in invasiveness (p = 0.06). Treatment with different concentrations of aprotinin significantly decreased the surviving fraction and inhibited the growth of all cell lines tested in this study (analysis of variance (ANOVA) p < 0.001). Compared to cancer cell lines, normal HDF-1 cell line showed less sensitivity to antiproliferative effects of aprotinin, both in low and high doses.
Conclusion. Aprotinin significantly inhibited the growth of human breast cancer cell lines MDA-MB-231, SK-BR-3 and MCF-7, and normal fibroblast cell line HDF-1. The growth inhibitory effect was more dominant in cancer cell lines. Inhibition of local invasion by aprotinin was significant only in the case of MDA-MB-231. Future molecular studies could shed further lights on mechanisms underlying antineoplastic effects of aprotinin and its potential therapeutic effects.

Key words

breast cancer, in vitro, cell proliferation, aprotinin, neoplasm invasion

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