Biologically Active Peptide Combined With Oxaliplatin Inhibits The Expression Of NUSAP1 In Gastric Cancer And Its Mechanism Of Action

Objective: Gastric carcinoma is one of the main causes of cancer related deaths worldwide,no specificity,low diagnosis rate.Chemotherapy is one of the main treatments of advanced gastric cancer,chemotherapeutic drugs cause the patient’s prognosis due to the cause of drug resistance due to its choice of low-toxic side effects.The biological activated peptide used in this topic is a low molecular weight biologically active substance prepared by the goat liver,named an anti-cancer bioactive peptide.ABP has anti-cancer effects in induced apoptosis,inhibiting cell proliferation,stem cell charact--eristics,angiogenesis in tumor cells.To verify that ABP combined with oxaliplatin can inhibit the expression of NUSAP1 in gastric cancer and explore the mechanism of inhibition of NUSAP1 expression in gastric cancer.Screening of gastric cancer targets,exploring safety and effective combina--tion treatment methods.Methods: The expression of NUSAP1 in human different cancers,gastric cancer,and normal gastric tissue is determined by bioinformatics database.(Http://gepia.cancer-pku.cn/).Human gastric cancer cell lines MKN45 and AGS were cultured using in vitro cell culture technology.According to the team’s early IC50 test results,85% of the fused cells were treated with ABP and OXA drugs.The changes of NUSAP1 transcription level in MKN45 cells and AGS cells treated with ABP,OXA and A-O for 24 h were detected by qRT-PCR.Changes in NUSAP1 protein expression in AGS/MKN45 cells were detected by Western Blotting methods for 24 hours of treatment 24 h.Whether the decreased expression of NUSAP1 can inhibit the metastasis of gastric cancer cells by inhibiting the activation of Wnt/β-catenin signaling pathway and the epithelial mesenchymal transformation process.By establishing an animal model of gastric cancer push nude mice,the effect of applying ABP,OXA,and A-O for the body weight and tumor volume of nude mice is judged,and the treatment effect of the drug is applied to the tumor nude mice.The changes of tumor histological structure in nude mice were detected by HE.The expression of NUSAP1 in tumor tissues of different groups was detected by immunohistochemical method.Results:(1)GEPIA website data analysis proves that NUSAP1 has high expression in a variety of cancer in humans;significantly increased in gastric cancer tissues(P <0.01).(2)qRT-PCR/Western Blotting showed that the mRNA transcription and protein expression of NUSAP1 in human gastric cancer MKN45 cells and AGS cells were decreased by ABP alone and A-O(P<0.05).(3)The decreased expression of Nus AP1 may inhibit the expression of β-catenin and TCF1 in the Wnt/β-catenin signaling pathway,and then inhibit the expression of its downstream target factors Met,Cy CD1 and c-myc to inhibit the malignant transformation of gastric cancer cells.(4)ABP,OXA alone and A-O may inhibit the metastasis of gastric cancer cells by inhibiting the EMT process.Conclusion:(1)NUSAP1 is highly expressed in human gastric cancer tissues,nude mouse tumor-bearing tissues and human gastric cancer cells.(2)ABP,OXA and A-O all inhibited the expression of NUSAP1 in gastric cancer cells and tumor-bearing tumor tissues of nude mice.The toxic effects of OXA can be reduced by halving the dose used.(3)It has been preliminarily proved that ABP and A-O can inhibit the expression of NUSAP1,inhibit the activation of Wnt/β-catenin pathway and inhibit the EMT process,and finally inhibit the progression of gastric cancer.