Abstract: Abstract: Objective To investigate the inhibition effects of apatinib on human colon cancer cells HCT116 p53+/+and
HCT116 p53-/-, and further explore the molecular mechanisms in vitro. Methods The gradient concentrations of apatinib
(0, 15,30 and 60 μmol/L) were used to treat HCT116 p53+/+ and HCT116 p53-/- for 24 h and 48 h. The inhibitory effects of
apatinib on the proliferation of two cell lines were detected by CCK-8. Flow cytometry (Annexin V/PI method) was used to
detect the apoptosis rates of apatinib treated HCT116 p53+/+ and HCT116 p53-/-cells. The expression levels of p53, NF-κB
p65, Caspase-3 mRNA and protein of apatinib treated HCT116 p53+/+ and HCT116 p53-/-cells were revealed by real-time
PCR and Western blot assay. Results CCK-8 results showed that apatinib could inhibit the viability of HCT116 p53+/+ and
HCT116 p53-/-cells in a dose-dependent manner (P＜0.01). Flow cytometry results showed that after treatment with
apatinib, the apoptosis rates of HCT116 p53+/+ and HCT116 p53-/-cells were increased (P＜0.01). Compared with HCT116
p53+/+ , the pro-apoptotic effect of apatinib on HCT116 p53-/- was lower (P＜0.05). After treatment with apatinib, the
expression levels of p53, NF- κB p65, capsase-3 mRNA and Caspase-3 protein were increased in HCT116 p53+/+ and
HCT116 p53-/-cells (P＜0.05). After treatment with apatinib, the protein expressions of p53 and NF- κB p65 were downregulated in HCT116 p53+/+ cells, while the protein expression of NF-κB p65 was up-regulated in HCT116 p53-/- cells (P＜
0.01). Conclusion Apatinib could inhibit cell proliferation and promote the apoptosis of HCT116 p53+/+ and HCT116
p53-/- cells through p53/NF-κB pathway. Colorectal cancer cells may develop drug resistance to apatinib through HCT116
p53-/- cells.

Key words: colonic neoplasms;HCT116 cells, genes, p53, NF-kappa B, transcription factor RelA, cell proliferation, apoptosis, apatinib