To investigate the effect of apatinib, a small-molecule tyrosine kinase inhibitor, combined with 5-FU on proliferation, apoptosis and invasiveness of human gastric cancer cells AGS, and provide experimental basis for the treatment of two drugs combination in gastric cancer in clinic.
The expression of vascular endothelial growth factor receptor 2 (VEGFR2) protein in human umbilical vein endothelial cells (HUVEC) and human gastric cancer cells were assessed by western blotting. 4-methyl-teerazolium (MTT) assay and flow cytometry were used to assess the cytotoxicity and apoptosis effects of the cells in response to control, single apatinib, single 5-FU, and apatinib combined 5-FU groups. Western blotting was used to evaluate the expression of p-Akt, proliferating cell nuclear antigen (PCNA), Caspase-3 and the invasiveness differences of the four groups were detected by wound healing assay and matrix metalloprotein-2 (MMP-2), E-cadherin gene amplification were measured by RT-PCR.
AGS had the expression of VEGFR2. Compared with single drug groups, apatinib combined with 5-FU could significantly suppress the growth, proliferation and induce apoptosis of human gastric cancer cells in time and dose-dependent manners (P
Our study points that apatinib combined 5-FU could inhibit the proliferation of AGS gastric cancer cells by down-regulating the expression of p-Akt. The invasiveness of AGS cancer cell was inhibited by reduced expression of MMP-2 and E-cadherin genes, and provides a theory basis for 5-FU and apatinib combination in clinic with advanced gastric cancer patients who failed to second-line treatment but still had a good performance status.
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Legal entity responsible for the study
National Nature Science Foundation of China
All authors have declared no conflicts of interest.