| Every year approximately 990000 people are diagnosed with gastric cancer worldwide,of whom about738000 die from this disease,making gastric cancer the 4th most common incident cancer and the 2nd most common cause of cancer death.The early symptoms of gastric cancer are not obvious,more than 80%of the patients with gastric cancer in China are in the late stage of diagnosis,and the prognosis is poor.The invasion and metastasis of malignant tumor is the leading cause of death in Cancer patients and its mechanism is complex.The tumor cells in the primary site are separated from the primary focus,invading through the basement membrane and infiltrating and growing into the surrouding stroma,passing through the local capillaries or lymphatic walls into the lumen.Aggregation with platelets or formation of small tumor thrombus,with the transport of blood or lymph to the capillary bed of the target organ,adhesion to the vascular or lymphatic endothelial cells in that part,passing through the tubewall and basement membrane into the surrounding stroma,the metastasis of tumor cells is formed by increasing the value of tumor cells at the secondary site.About 90%of malignant tumors come from epithelial tissue.The most important morphological change in tumor maligant transformation is from the highly differentiated epithelial cell morphology to the appearance of migration and invasion phenotypes,whic is called Epithelial-mesenchymal transition(EMT).In this process,the cells gradually reorganize or down-regulate their own parietal and basal epithelial specific tight junction proteins(such as E-cadherin)and overexpression of mesenchymal molecules such as Vimentin and N-cadherin.It will lead to the loss of connections between cells and the enhancement of cell motility,which is necessary change in invasion.When phenotypic cells with high migration and invasion ability appear,they will cause tumor cells to penetrate the basement membrane barrier and invade adjacent tissues,which was considered to be a important step in tumor metastasis.The dissolution of cell matrix proteins by some specific proteolytic enzymes,such as matrix metalloproteinases(MMPs),is the primary condition for tumor invasion.Studies have shown that MMPs can directly regulate the adhesion and migration of tumor cells by shearing cell-cell and cell-matrix receptors.Among them,MMP-9 is considered to be one of the key enzymes in the process of tumor invasion and metastasis.Xiaoaiping,extracted from Marsdenia tenacissima(Asclepiadaceae),is a Chinese medicine whose main ingredient is the glaucescent fissistigma root.Previous studies have shown that XAP has anti-invasion and anti-proliferation effects on different types of cancer,including gastric cancer,liver cancer,lung cancer,colorectal cancer,cervical cancer,leukaemia and other malignant tumours.S-1 is a new type of 5-fluorouracil(5-fu)-derived chemotherapeutic drug that is recognized as one of the standard chemotherapeutic agents for gastric cancer.It has been reported to be well tolerated and active against solid cancers.The antitumour mechanism of S-1 is to inhibit proliferation,promote apoptosis and reduce the invasiveness of tumour cells.Drug therapy is an effective antitumour method in which the combined use of drugs is particularly important.The combination of Chinese and Western medicine in the treatment of gastric cancer can play a synergistic role and has certain advantages in reducing the focus and improving the symptoms and survival times of patients and increasing patient tolerance of chemotherapeutics.Prior studies that have noted the importance of the combined use of XAP and chemotherapeutic drugs which can enhance the antitumour effect.However,XAP combined with S-1 has not yet been studied.The present study was designed to determine the effects of XAP combined with S-1 on the invasion and metastasis of human gastric cancer BGC-823 and MGC-803 cells and to explore its mechanism. |
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