title: [Effects of LCL161, a Smac mimetic on the proliferation and apoptosis in hepatocellular carcinoma cells].
abstract: OBJECTIVE
  To investigate the effects of LCL161, a Smac mimetic, on the proliferation and apoptosis in hepatocellular carcinoma cells and the underlying mechanisms.
  
  
  METHODS
  The effect of LCL161 on the cell viability of HepG2 and SMMC7721 cells was measured by MTT assay. The effect of LCL161 at lower concentrations on the proliferation in hepatocellular carcinoma (HCC) cells was detected by colony formation assay. Apoptosis was assessed by flow cytometry with PI staining. The mitochondrial membrane potential was measured by JC-1 staining. The expression of PARP, p-Akt, cIAP1 and XIAP protein was analyzed by Western blot.
  
  
  RESULTS
  LCL161 displayed notable antiproliferative activity on HCC cells at the concentrations of 1-16 μmol/L (P<0.01), with IC50 values of 4.3 and 4.9 μmol/L for HepG2 and SMMC7721 cells, respectively, after treatment for 48 h. LCL161 at lower concentrations obviously inhibited the colony formation of HCC cells. LCL161 induced significant apoptosis in HCC cells (P<0.01), and resulted in the apoptotic rate at (1.5±0.8)% or (1.8±0.6)% , (15.2±2.8)% or (12.2±2.4)%, (28.7±3.0)% or (22.4±2.7)%, (34.6±2.3)% or (30.2±2.4)% for HepG2 cells or SMMC7721 cells at the concentration of 0, 2, 4 or 8 μmol/L, respectively. The result of JC-1 staining indicated that the mitochondrial membrane potential of HCC cells was reduced by LCL161. In addition, LCL161 promoted the cleavage of PARP, down-regulated the protein expression of p-Akt, and degraded cIAP1.
  
  
  CONCLUSIONS
  LCL161 possesses significant anti-proliferative activity and pro-apoptotic action in HepG2 and SMMC7721 cells, which might be correlated with reduction in mitochondrial membrane potential, down-regulation of p-Akt and degradation of cIAP1.
authors.affiliation: Department of Pharmacy, Bengbu Medical College; Anhui Engineering Technology Research Center of Biochemical Pharmaceutics, Bengbu Anhui 233030, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Ren
authors.affiliation: Department of Pharmacy, Bengbu Medical College; Anhui Engineering Technology Research Center of Biochemical Pharmaceutics, Bengbu Anhui 233030, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Bengbu Medical College; Anhui Engineering Technology Research Center of Biochemical Pharmaceutics, Bengbu Anhui 233030, China.
authors.forename: Dianlong
authors.initials: D
authors.lastname: Chong
authors.affiliation: Department of Pharmacy, Bengbu Medical College; Anhui Engineering Technology Research Center of Biochemical Pharmaceutics, Bengbu Anhui 233030, China.
authors.forename: Zhirui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Bengbu Medical College; Anhui Engineering Technology Research Center of Biochemical Pharmaceutics, Bengbu Anhui 233030, China.
authors.forename: Can
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Bengbu Medical College; Anhui Engineering Technology Research Center of Biochemical Pharmaceutics, Bengbu Anhui 233030, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Bengbu Medical College; Anhui Engineering Technology Research Center of Biochemical Pharmaceutics, Bengbu Anhui 233030, China.
authors.forename: Surong
authors.initials: S
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D015536:Down-Regulation; D056945:Hep G2 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008113:Liver Neoplasms; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D013844:Thiazoles / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein
chemical_list: D051034:Inhibitor of Apoptosis Proteins; C574246:LCL161; D013844:Thiazoles; D051636:X-Linked Inhibitor of Apoptosis Protein; C494833:BIRC2 protein, human; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt