Abstract

Background: This study aimed to determine the effect and mechanism of Xiaoaiping (XAP) injection combined with S-1 in inhibiting the invasion and metastasis of human GC cells.

Methods: BGC-823 and MGC-803 cells were incubated in vitro, and the effects of treatment on the cytotoxicity and proliferation of BGC-823 and MGC-803 cells were evaluated by MTT assay. Cell adhesion tests and Transwell assays were used to detect the effects of Xiaoaiping injection combined with S-1 on the metastatic ability of BGC-823 and MGC-803 cells. The expression of VEGF, Metalloproteinases (MMPs) and proteins related to the Epithelial-Mesenchymal Transition (EMT) were detected by Western blotting. Meanwhile, a tumour model was established in nude mice, and the effect of XAP combined with S-1 on BGC-823 cells in vivo was studied.

Results: Compared with the single drug group, the combination of XAP with S-1 increased the inhibition rate (P<0.05). The adhesion test showed that the combination group significantly inhibited the adhesion of BGC-823 and MGC-803 cells (P<0.05). The combination of XAP with S-1 reduced the migration and invasion potential of human GC BGC-823 and MGC-803 cells. Western blotting showed that the expression of VEGF, MMP-9, Ncadherin and vimentin was decreased and E-cadherin expression was increased in the combination group compared with these expression values in either the XAP or S-1 alone group (P<0.05). In vivo, we found that XAP combined with S-1 had a significant inhibitory effect on the growth of tumours compared with XAP or S-1 alone. Immunohistochemistry showed that XAP combined with S-1 was able to enhance the levels of E-cadherin and downregulate N-cadherin and vimentin.

Conclusion: The combination of XAP with S-1 can enhance the inhibitory effect of a single drug on proliferation, invasion and metastasis. The mechanism may be related to the decrease in the expression of VEGF and MMP-9 proteins and the effect on EMT.

Keywords: Xiaoaiping (XAP) injection, S-1, invasion and metastasis, GC, MMP-9, VEGF, Epithelial-Mesenchymal Transition (EMT).