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

  • Authors:
    • 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
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, ‘Angelo Nocivelli’ Institute for Molecular Medicine, University of Brescia, I‑25123 Brescia, Italy, Department of Oncology, Flow Cytometry Unit, IRCCS - ‘Mario Negri’ Institute for Pharmacological Research, I‑20156 Milan, Italy, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA
    Copyright: © Bandiera et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2493-2500
    |
    Published online on: August 16, 2016
       https://doi.org/10.3892/ol.2016.5008
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Bandiera E, Todeschini P, Romani C, Zanotti L, Erba E, Colmegna B, Bignotti E, Santin AD, Sartori E, Odicino FE, Odicino FE, et al: The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines. Oncol Lett 12: 2493-2500, 2016.
APA
Bandiera, E., Todeschini, P., Romani, C., Zanotti, L., Erba, E., Colmegna, B. ... Ravaggi, A. (2016). The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines. Oncology Letters, 12, 2493-2500. https://doi.org/10.3892/ol.2016.5008
MLA
Bandiera, E., Todeschini, P., Romani, C., Zanotti, L., Erba, E., Colmegna, B., Bignotti, E., Santin, A. D., Sartori, E., Odicino, F. E., Pecorelli, S., Tassi, R. A., Ravaggi, A."The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines". Oncology Letters 12.4 (2016): 2493-2500.
Chicago
Bandiera, E., Todeschini, P., Romani, C., Zanotti, L., Erba, E., Colmegna, B., Bignotti, E., Santin, A. D., Sartori, E., Odicino, F. E., Pecorelli, S., Tassi, R. A., Ravaggi, A."The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines". Oncology Letters 12, no. 4 (2016): 2493-2500. https://doi.org/10.3892/ol.2016.5008
Copy and paste a formatted citation
x
Spandidos Publications style
Bandiera E, Todeschini P, Romani C, Zanotti L, Erba E, Colmegna B, Bignotti E, Santin AD, Sartori E, Odicino FE, Odicino FE, et al: The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines. Oncol Lett 12: 2493-2500, 2016.
APA
Bandiera, E., Todeschini, P., Romani, C., Zanotti, L., Erba, E., Colmegna, B. ... Ravaggi, A. (2016). The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines. Oncology Letters, 12, 2493-2500. https://doi.org/10.3892/ol.2016.5008
MLA
Bandiera, E., Todeschini, P., Romani, C., Zanotti, L., Erba, E., Colmegna, B., Bignotti, E., Santin, A. D., Sartori, E., Odicino, F. E., Pecorelli, S., Tassi, R. A., Ravaggi, A."The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines". Oncology Letters 12.4 (2016): 2493-2500.
Chicago
Bandiera, E., Todeschini, P., Romani, C., Zanotti, L., Erba, E., Colmegna, B., Bignotti, E., Santin, A. D., Sartori, E., Odicino, F. E., Pecorelli, S., Tassi, R. A., Ravaggi, A."The HIV‑protease inhibitor saquinavir reduces proliferation, invasion and clonogenicity in cervical cancer cell lines". Oncology Letters 12, no. 4 (2016): 2493-2500. https://doi.org/10.3892/ol.2016.5008
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