Inhibitory Effects of Apatinib Combined With Shen Yi Capsule on the Proliferation of Gastric Adenocarcinoma Cells SGC-7901 and its Possible Mechanism

Objective To evaluate the inhibitory effects of apatinib combined with Shen Yi Capsules of VEGFR-2 high expression of gastric adenocarcinoma cells and explore its mechanism of promoting apoptosis.

Methods Select different human gastric adenocarcinoma cells SGC-7901、AGS、MKN-45、MGC-803 and human venous cells HUVEC(blank control group)for cultivator-PCR was used to screens the gastric adenocarcinoma cell with high VEGFR-2 expression on mRNA levels. The expression of VEGFR-2 high expression of gastric adenocarcinoma cells detection of related proteins was explored by western blotting. The MTT assay was used to detect the inhibiting effect of different concentrations of apatinib, Shen Yi Capsules and apatinib combined with Shen Yi Capsules on the proliferation of VEGFR-2 high expression of gastric adenocarcinoma cells, to determine the effective inhibitory concentration of medicines. To utilize the principle of intermediate to draw the Fa-CI curves, to evaluate the mechanism of combined action between the apatinib and Shen Yi Capsule. Annexin V-FITC/PI was performed to investigate the apoptosis of VEGFR-2 high expression gastric adenocarcinoma cells at the group of control, apatinib, Shen Yi Capsule and apatinib combined with Shen Yi Capsule. Immunohistochemical methods was investigate the distribution of apoptosis related proteins about Bcl-2, Bax, Fas.

Results The RT-PCT and western blotting results that the gastric adenocarcinoma cells SGC-7901 was all highly expressed on the levels of VEGFR-2 mRNA and protein (P < 0.000 1). The MTT showed that the inhibitory cell proliferation concentration was that apatinib: 16 μg/mL, Shen Yi Capsule: 64 μg/mL, and according to the principle of intermediate effect, the combination index CI < 1, means that the combination of apatinib and Shen Yi Capsule was synergistic. Annexin V-FITC/PI results showed that the apoptosis rate of apatinib combined Shen Yi Capsule vs. apatinib, Shen Yi Capsule was significantly increased (P < 0.05). Immunohistochemical methods was found that the group of apatinib combined Shen Yi Capsule increased the distribution of apoptosis-related proteins Bcl-2, Bax, Fas.

Conclusions Apatinib combined with Shen Yi Capsule have synergistic inhibitory effect on gastric adenocarcinoma cells SGC-7901, and the synergistic mechanism maybe related to up-regulating expression of apoptosis related proteins that Bcl-2, Bax, Fas, and to induction of gastric apoptosis adenocarcinoma cells by sensitize the programmed mitochondrial death.