Inhibition of MMP-9 expression by ritonavir or saquinavir is associated with inactivation of the AKT/Fra-1 pathway in cervical intraepithelial neoplasia cells

Bacigalupo,Ilaria; Palladino,Clelia; Leone,Patrizia; Toschi,Elena; Sgadari,Cecilia; Ensoli,Barbara; Barillari,Giovanni

doi:10.3892/ol.2017.5835

Inhibition of MMP-9 expression by ritonavir or saquinavir is associated with inactivation of the AKT/Fra-1 pathway in cervical intraepithelial neoplasia cells

Authors:
- Ilaria Bacigalupo
- Clelia Palladino
- Patrizia Leone
- Elena Toschi
- Cecilia Sgadari
- Barbara Ensoli
- Giovanni Barillari
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Affiliations: National Acquired Immune Deficiency Syndrome Center, National Institute of Health, I‑00161 Rome, Italy, Department of Haematology, Oncology and Molecular Medicine, National Institute of Health, I‑00161 Rome, Italy, Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, I‑00133 Rome, Italy
Published online on: March 9, 2017 https://doi.org/10.3892/ol.2017.5835
Pages: 2903-2908
Copyright: © Bacigalupo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A reduced incidence and decreased clinical progression of uterine cervical intraepithelial neoplasia (CIN) has been observed in women infected with human immunodeficiency virus (HIV) treated with HIV‑protease inhibitors (PIs). The HIV‑PIs saquinavir (SQV) and ritonavir (RTV) have been demonstrated to efficiently inhibit invasion of human primary CIN cells by downregulating the expression of matrix metalloproteinase (MMP)‑9. The present study further investigated the molecular mechanisms underlying the activity of SQV and RTV in CIN. The results of the present study indicate that the treatment of human primary CIN cells with SQV or RTV directly impairs events leading to MMP‑9 expression, including the phosphorylation of AKT and the nuclear localisation of the Fos‑related antigen transcription factor. In addition, neither SQV nor RTV affected the expression of human papilloma virus proteins, such as E6 or E7. In view of the important role that the AKT/Fra‑1/MMP‑9 signalling pathway serves in CIN progression to invasive cervical carcinoma, these data further support the use of HIV‑PIs in the treatment of CIN in women infected with HIV and women who are not infected with HIV. Furthermore, the present study identified a molecular mechanism underlying the anti‑invasive effects of SQV/RTV, providing useful information for the development of SQV/RTV derivatives, which may be employed as novel anticancer drugs.

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