title: [Inhibitory effect of apatinib on HCT-116 cells and its mechanism].
abstract: OBJECTIVE
  To investigate the inhibitory effects of apatinib on colorectal carcinoma HCT-116 cells in vitro and the signaling pathways involved.
  
  
  METHODS
  The cytotoxicity of different concentrations (0, 0.5, 1, 1.5, and 2 µmol/L) of apatinib in HCT-116 cells was assessed by MTT assay, using capecitabine as the positive control. The apoptosis rate of apatinib-treated HCT-116 cells was detected using flow cytometry, and the expressions of Bcl-2, Bax, and caspase-3 were determined with quantitative real-time PCR and Western blotting. The effect of apatinib on the expressions of Akt, pAkt, Erk1/2 and pErk1/2 in HCT-116 cells was evaluated using Western blotting.
  
  
  RESULTS
  Apatinib significantly inhibited the proliferation of HCT-116 cells in a concentration-dependent manner with an IC50value of 1.335 µmol/L. Flow cytometric analysis showed that apatinib significantly increased the apoptotic rate of HCT-116 cells dose-dependently. Apatinib induced the expression of the pro-apoptotic genes Bax and caspase-3 at both the mRNA and protein levels while inhibited the expression of the anti- apoptotic gene Bcl-2. The expressions of p-Akt and p-Erk1/2 were decreased in HCT-116 cells after apatinib treatment, but the total protein levels did not undergo obvious changes.
  
  
  CONCLUSIONS
  Apatinib inhibits the proliferation and induces apoptosis of HCT-116 cells by suppressing the phosphorylation of Erk1/2 and Akt in the MAPK/Erk and PI3K/Akt signaling pathways.
authors.affiliation: Department of Oncology, First Affiliated Hospital of Kunming Medical University, Kunming 650032.E-mail: ynyinliang@126.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Yin
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Feng-Chang
authors.initials: FC
authors.lastname: Huang
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Zheng-Qi
authors.initials: ZQ
authors.lastname: Wen
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Dong
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D045325:HCT116 Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D051028:bcl-2-Associated X Protein; C553458:apatinib; D019869:Phosphatidylinositol 3-Kinases; C505407:CASP3 protein, human; D053148:Caspase 3