title: Nelfinavir is effective against human cervical cancer cells in vivo: a potential treatment modality in resource-limited settings.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gynecologic Oncology, Department of Reproductive Medicine, Rebecca and John UCSD Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Mitzie-Ann
authors.initials: MA
authors.lastname: Davis
authors.affiliation: Division of Gynecologic Oncology, Department of Reproductive Medicine, Rebecca and John UCSD Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Joe R
authors.initials: JR
authors.lastname: Delaney
authors.affiliation: Division of Gynecologic Oncology, Department of Reproductive Medicine, Rebecca and John UCSD Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Chandni B
authors.initials: CB
authors.lastname: Patel
authors.affiliation: Division of Gynecologic Oncology, Department of Reproductive Medicine, Rebecca and John UCSD Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Storgard
authors.affiliation: Division of Gynecologic Oncology, Department of Reproductive Medicine, Rebecca and John UCSD Moores Cancer Center, La Jolla, CA, USA.
authors.forename: Dwayne G
authors.initials: DG
authors.lastname: Stupack
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019888:Nelfinavir / Q000737:chemistry / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D019888:Nelfinavir; D002945:Cisplatin
keywords: autophagy; cervical cancer; cisplatin resistance; nelfinavir; responsible medicine