Nelfinavir is effective against human cervical cancer cells in vivo: a potential treatment modality in resource-limited settings
Authors Davis M, Delaney JR, Patel C, Storgard R, Stupack D
Received 10 December 2015
Accepted for publication 25 February 2016
Published 2 June 2016 Volume 2016:10 Pages 1837—1846
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Wei Duan
Mitzie-Ann Davis,* Joe R Delaney,* Chandni B Patel, Ryan Storgard, Dwayne G Stupack
Division of Gynecologic Oncology, Department of Reproductive Medicine, Rebecca and John UCSD Moores Cancer Center, La Jolla, CA, USA
*These authors contributed equally to this work
Objective: The standard treatment for cervical cancer in developed countries includes surgery and chemoradiation, with standard of care lagging in developing countries. Even in the former case, treatment frequently yields recalcitrant tumors and women succumb to disease. Here we examine the impact of nelfinavir, an off-patent viral protease inhibitor, which has shown promise as an antineoplastic agent.
Methods: We evaluated the morphological and proliferative effects of the autophagy-stressing drug nelfinavir in normal and cisplatin-resistant cervical cancer cells. Immunofluorescent validation of autophagy markers was performed and the impact of nelfinavir in an in vivo model of tumor growth was determined.
Results: Nelfinavir exhibits cytotoxicity against both cisplatin-sensitive and -resistant ME-180 human cervical cancer cells in vitro and in vivo. Immunoblotting and immunofluorescence showed an expression of the autophagy marker LC3-II in response to nelfinavir treatment.
Conclusion: Nelfinavir, now available as an inexpensive generic orally dosed agent (Nelvir), is cytotoxic against cervical cancer cells. It acts by burdening the autophagy pathway to impair tumor cell survival and a modest induction of apoptosis. While further studies are needed to elucidate the optimal method of application of nelfinavir, it may represent an appealing global option for the treatment of cervical cancer.
Keywords: cervical cancer, nelfinavir, cisplatin resistance, autophagy, responsible medicine
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