The Effect Of Anlotinib On The Biological Function Of Gastric Cancer Cells And Its Mechanism

Objective To investigate the effect of anlotinib on the biological characteristics of gastric cancer cells and discover its possible molecular mechanism.Methods The effect of anlotinib on the proliferation,migration and invasion ability of gastric cancer cells was detected by CCK-8 assay,Wound-Healing and Transwell assay.The cell apoptosis was detected by Hoechst 33342 fluorescence staining.Using TRIzo to extract total cellular RNA to RNA sequencing.Used DESeq2 package to find differentially expressed genes,and cluster Profiler package was used to gene functional analysis.Used MCC algorithm of the Cytohubba plugin and r MATS software to find key interact proteins and alternative splicing analysis.Results Anlotinib inhibited the viability of gastric cancer cells in a dosedependent and time-dependent manner.Anlotinib inhibit the cell migration and invasion and promote cell apoptosis.After BGC-823 treated with anlotinib,1549 differentially expressed genes(275 up-regulated,1274 down-regulated)were founded.GO analysis showed that anlotinib affected the biological processes,such as sterol biosynthetic process,cholesterol biosynthetic process,secondary alcohol biosynthetic process;about the cellular components,it affected condensed nuclear chromosome kinetochore,microvillus,apical part of cell etc.KEGG pathway enrichment analysis indicated that Anlotinib affected pathways such as cell cycle,arachidonic acid metabolism and Steroid biosynthesis.CDC20,CCNB1,STK6,PTTG1,HMMR,KIF20 A,CEP55,DLGAP5,PLK1 and CKS2 are the key interacting proteins.The metabolic pathways,lysosome may be effected when genes are alternative splicing.The target gene of anlotinib PDGFRB was downregulated.The higher expression of PDGFRB was related to the clinical progression and not benefit to the prognosis of gastric cancer patients.Conclusion Anlotinib inhibited the proliferation,migration and invasion and promoted cell apoptosis of gastric cancer cells.Anlotinib may achieve the anti-tumor effect in gastric cancer by regulating the expression of related genes and related pathways.Figure 13;Table 6;Reference 142...