A Study on the Effect and Mechanism of Xiaoaiping (XAP) Injection and S-1 Combination Therapy in Inhibiting the Invasion and Metastasis of Human GC Cells

Author(s):

Peiyu Wen, Haibo Wang, Tengyang Ni, Xiaojun Dai, Zewen Chu, Shuang Ma, Liangliang Xiang, Zhen Zhou, Yayun Qian, Masataka Sunagawa and Yanqing Liu*   Pages 1037 - 1046 ( 10 )

Abstract:

<P>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. </P><P> 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. </P><P> 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. </P><P> 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.</P>

Keywords:

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

Affiliation:

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, Department of physiology, School of Medicine, Showa University, Tokyo 142, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001

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