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.