The HIV-protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines

Elisabetta Bandiera, Paola Todeschini, Chiara Romani, Laura Zanotti, Eugenio Erba, Benedetta Colmegna, Eliana Bignotti, Alessandro Davide Santin, Enrico Sartori, Franco Edoardo Odicino, Sergio Pecorelli, Renata Alessandra Tassi, Antonella Ravaggi

Research output: Contribution to journalArticlepeer-review

Abstract

Innovative therapies in cervical cancer (CC) remain a priority. Recent data indicate that human immunodeficiency virus (HIV)-protease inhibitors used in highly active antiretroviral therapy can exert direct antitumor activities also in HIV-free preclinical and clinical models. The aim of the present study was to evaluate the antineoplastic effects of various HIV-protease inhibitors (indinavir, ritonavir and saquinavir) on primary and established CC cell lines. Two CC cell lines established in our laboratory and four commercially available CC cell lines were treated with indinavir, ritonavir and saquinavir at different concentrations and for different times. Proliferation, clonogenicity and radiosensitivity were evaluated by crystal violet staining. Proteasomal activities were assessed using a cell-based assay and immunoblotting. Cell cycle was analyzed by propidium iodide staining and flow cytometric analysis. Invasion was tested with Matrigel chambers. A t-test for paired samples was used for statistical analysis. In all cell lines, saquinavir was more effective than ritonavir in reducing cell proliferation and inhibiting proteasomal activities (P≤0.05). Conversely, indinavir exerted a negligible effect. The saquinavir concentrations required to modulate the proteasome activities were higher than those observed to be effective in inhibiting cell proliferation. In HeLa cells, saquinavir was strongly effective in inhibiting cell invasion and clonogenicity (P≤0.05) at concentrations much lower than those required to perturb proteasomal activities. Saquinavir did not contribute to increase the sensitivity of HeLa cells to X-rays. In conclusion, the present results demonstrate that saquinavir is able to significantly reduce cell proliferation, cell invasion and clonogenicity in a proteasome-independent manner in in vitro models of CC, and suggest that saquinavir could be a promising CC therapeutic agent.

Original languageEnglish
Pages (from-to)2493-2500
Number of pages8
JournalOncology Letters
Volume12
Issue number4
DOIs
Publication statusPublished - Oct 1 2016

Keywords

  • Cell lines
  • Cervical cancer
  • HIV-protease inhibitors
  • Proteasomal activities
  • Saquinavir

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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