A PTEN inhibitor displays preclinical activity against hepatocarcinoma cells

Giuseppe Montalto, Maria Rita Emma, Melchiorre Cervello, Giuseppa Augello, Maria Rita Emma, Roberto Puleio, Antonella Cusimano, Guido R. Loria, James A. Mccubrey, Giuseppe Montalto, Antonella Cusimano, Giuseppa Augello

Risultato della ricerca: Articlepeer review

14 Citazioni (Scopus)

Abstract

Phosphatase and tensin homolog (PTEN) gene is considered a tumor suppressor gene. However, PTEN mutations rarely occur in hepatocellular carcinoma (HCC), whereas heterozygosity of PTEN, resulting in reduced PTEN expression, has been observed in 32–44% of HCC patients. In the present study, we investigated the effects of the small molecule PTEN inhibitor VO-OHpic in HCC cells. VO-OHpic inhibited cell viability, cell proliferation and colony formation, and induced senescence-associated β-galactosidase activity in Hep3B (low PTEN expression) and to a lesser extent in PLC/PRF/5 (high PTEN expression) cells, but not in PTEN-negative SNU475 cells. VO-OHpic synergistically inhibited cell viability when combined with PI3K/mTOR and RAF/MEK/ERK pathway inhibitors, but only in Hep3B cells, and significantly inhibited tumor growth in nude mice bearing xenografts of Hep3B cells. Therefore, we demonstrated for the first time that VO-OHpic inhibited cell growth and induced senescence in HCC cells with low PTEN expression, and that the combination of VO-OHpic with PI3K/mTOR and RAF/MEK/ERK inhibitors resulted in a more effective tumor cell kill. Our findings, hence, provide proof-of-principle evidence that pharmacological inhibition of PTEN may represent a promising approach for HCC therapy in a subclass of patients with a low PTEN expression.
Lingua originaleEnglish
pagine (da-a)573-583
Numero di pagine11
RivistaCell Cycle
Volume15
Stato di pubblicazionePublished - 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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