title: Down-regulation of phosphoglucose isomerase/autocrine motility factor enhances gensenoside Rh2 pharmacological action on leukemia KG1α cells.
abstract: OBJECTIVE
  Ginsenoside Rh2, which exerts the potent anticancer action both in vitro and in vivo, is one of the most well characterized ginsenosides extracted from ginseng. Although its effects on cancer are significant, the underlying mechanisms remain unknown. In this study, we sought to elucidate possible links between ginsenoside Rh2 and phosphoglucose isomerase/autocrine motility factor (PGI/AMF).
  
  
  METHODS
  KG1α, a leukemia cell line highly expressing PGI/AMF was assessed by western blot analysis and reverse transcription- PCR (RT-PCR) assay after transfection of a small interfering (si)-RNA to silence PGI/AMF. The effect of PGI/ AMF on proliferation was measured by typan blue assay and antibody array. A cell counting kit (CCK)-8 and flow cytometry (FCM) were adopted to investigate the effects of Rh2 on PGI/AMF. The relationships between PGI/AMF and Rh2 associated with Akt, mTOR, Raptor, Rag were detected by western blot analysis.
  
  
  RESULTS
  KG1α cells expressed PGI/AMF and its down-regulation significantly inhibited proliferation. The antibody array indicated that the probable mechanism was reduced expression of PARP, State1, SAPK/JNK and Erk1/2, while those of PRAS40 and p38 were up-regulated. Silencing of PGI/AMF enhanced the sensibility of KG1α to Rh2 by suppressing the expression of mTOR, Raptor and Akt.
  
  
  CONCLUSIONS
  These results suggested that ginsenoside Rh2 suppressed the proliferation of KG1α, the same as down-regulation of PGI/AMF. Down-regulation of PGI/ AMF enhanced the pharmacological effects of ginsenoside Rh2 on KG1α by reducing Akt/mTOR signaling.
authors.affiliation: Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, the First Affiliated Hospital, Chongqing Medical University, Chongqing, China E-mail : lijingyangyang@126.com.cn, chendilong@21cn.com.
authors.forename: Zhi-Mei
authors.initials: ZM
authors.lastname: You
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Liu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Di-Long
authors.initials: DL
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics*; D018922:HL-60 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D007938:Leukemia / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D005894:Panax / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt; D034622:RNA Interference; D034741:RNA, Small Interfering; D000076223:Regulatory-Associated Protein of mTOR; D050794:STAT1 Transcription Factor / Q000096:biosynthesis; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
chemical_list: C484523:AKT1S1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D018398:Homeodomain Proteins; D010936:Plant Extracts; D034741:RNA, Small Interfering; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C064658:RAG-1 protein; D011065:Poly(ADP-ribose) Polymerases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005956:Glucose-6-Phosphate Isomerase