title: Inhibition of Autophagy Increases Proliferation Inhibition and Apoptosis Induced by the PI3K/mTOR Inhibitor NVP-BEZ235 in Breast Cancer Cells.
abstract: BACKGROUND
  The phosphoinositide 3 kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) pathway is a complicated intracellular pathway which leads to cell growth and tumor proliferation and plays a significant role in breast cancer. Multiple compounds targeting this pathway are being evaluated in clinical trials. NVP-BEZ235, a novel and orally available dual PI3K/mTOR inhibitor, showed great antitumor effect and provided a therapy strategy in breast cancer.
  
  
  METHODS
  In this study, we detect the effect of NVP-BEZ235 on cell viability, apoptosis, and autophagy in a breast cancer cell line. We also test the effect of NVP-BEZ235 on the expression of PI3K/AKT/mTOR pathway proteins p-AKT, p-mTOR, and p-70S6K.
  
  
  RESULTS
  The results showed that the PI3K/AKT/mTOR proteins p-AKT, p-mTOR, and p-70S6K were obviously suppressed by NVP-BEZ235. NVP-BEZ235 inhibited cell proliferation and induced apoptosis and autophagy in breast cancer cells. In combination with autophagy inhibitors or autophagy gene knockdown, enhanced growth inhibition and apoptosis was induced by NVP-BEZ235 in MCF-7 cells.
  
  
  CONCLUSIONS
  This study provides a novel treatment strategy that PI3K/AKT/mTOR pathway inhibitors in combination with autophagy inhibitors lead to further apoptosis in breast cancer cells.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Ji
authors.forename: Wenyu
authors.initials: W
authors.lastname: Di
authors.forename: Qinghui
authors.initials: Q
authors.lastname: Yang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Lu
authors.forename: Weimei
authors.initials: W
authors.lastname: Cai
authors.forename: Jieqing
authors.initials: J
authors.lastname: Wu
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071193:Autophagy-Related Protein 7; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D061986:MCF-7 Cells; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D034622:RNA Interference; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism
chemical_list: D007093:Imidazoles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011804:Quinolines; C025946:3-methyladenine; D002738:Chloroquine; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D000225:Adenine; C531198:dactolisib