title: [Research on multiple myeloma cell apoptosis by inhibition of mTORC2 and chaperon pathways].
abstract: OBJECTIVE
  To explore apoptosis of multiple myeloma (MM) cells and its mechanism by the combined inhibition of mTORC2 signaling pathway and heat shock protein 90.
  
  
  METHODS
  The effects of Rapamycin, 17-AAG and the combination on proliferation of MM cell lines U266 and KM3 were assessed using MTT at different time points (0, 8, 24, 48 hour). Cell apoptosis and cell cycle distribution were measured by flow cytometry. The specific proteins p-AKT (ser473), p-AKT (thr450), p-S6 (S235/236) and AKT were detected by Western blotting.
  
  
  RESULTS
  Rapamycin, 17- AAG and the combination suppressed the proliferation of MM cell lines U266 and KM3, especially the combination of Rapamycin and 17-AAG synergistically inhibited the proliferation (P<0.05); Rapamycin induced G1 arrest both at 24 and 48 hours, 17-AAG also induced G1 arrest, especially at 48 hours (P<0.01); Rapamycin, 17-AAG alone decreased the expression of AKT and induced MM cell apoptosis to some extent (P<0.01); Chronic rapamycin treatment inhibited mTORC2; Inhibition of both mTORC2 and chaper on pathways degraded AKT and induced MM cell apoptosis, which was significantly higher than that of any single agent (P<0.01).
  
  
  CONCLUSIONS
  Inhibition of both mTORC2 and chaper on pathways decreased the expression of AKT to induce apoptosis of MM cells in vitro.
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Fu
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Ya'nan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha 410013, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gui
mesh_terms: D017209:Apoptosis; D016227:Benzoquinones / Q000494:pharmacology; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D000076225:Mechanistic Target of Rapamycin Complex 2; D009101:Multiple Myeloma / Q000473:pathology*; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D046912:Multiprotein Complexes; C112765:tanespimycin; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus