52PEffect of apatinib combined with 5-fluorouracil (5-FU) on proliferation, apoptosis and invasiveness of gastric cancer cells

Background: 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. Methods: 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. Results: 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<0.05). Western blotting dispalyed p-Akt and PCNA expression decreased after AGS cells treated with apatinb combined 5-FU. Wound-healing assay showed the invasiveness of AGS cells was inhibited and probably through down-regulating MMP-2 and E-cadherin amplification in combined group (P<0.05). Conclusions: 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. Legal entity responsible for the study: Bangwei Cao Funding: National Nature Science Foundation of China Disclosure: All authors have declared no conflicts of interest.