OBJECTIVE In order to investigate the possible anti-tumor molecular mechanisms of gecko polypeptide mixture(GPM).METHODS RNA-seq technology was used to identify the differentially expressed genes of human hepatocellular carcinoma(HCC)HepG2 cells treated with or without GPM.The HepG2 cells were treated with different concentration of GPM(0,0.1,0.2,0.3,0.4 mg·mL~(-1))for 6 h,12 h and 24 h,respectively.MTT assay was used to detect the viability of HepG2 cells.DAPI fluorescence staining was performed to observe nucleus morphological changes of HepG2 cells.Western blot analysis was applied to observe the expression of apoptosis-related proteins in HepG2 cells.RESULTS The results showed that GPM could induce HepG2 cells apoptosis and influence HepG2 cells proliferation in a dose-dependent manner.We applied many analysis methods,including differentially expressed genes analysis,Gene Ontology(GO)enrichment analysis,KEGG pathway enrichment analysis,protein-protein interaction network analysis to screen out possible molecular mechanisms.ER-nucleus signaling pathway,cellular response to stress and apoptotic processes were identified the potential anti-cancer molecular biological process of GPM.GPM may also induce apoptosis in HepG2 cells via endoplasmic reticulum stress pathway.The mechanism is closely related to ERs,which might be beneficial for clinical therapy of HCC.CONCLUSION GPM can inhibit cells proliferation and induce apoptosis in HepG2 cells.The gene expression profile of GPM in HepG2 cells was obtained.The present study revealed the potential anti-tumor mechanism of GPM. OBJECTIVE In order to investigate the possible anti-tumor molecular mechanisms of gecko polypeptide mixture (GPM). METHODS RNA-seq technology was used to identify the differentially expressed genes of human hepatocellular carcinoma (HCC) HepG2 cells treated with or without GPM. The HepG2 cells were treated with different concentrations of GPM (0,0.1,0.2,0.3,0.4 mg · mL -1) for 6 h, 12 h and 24 h, respectively. MTT assay was used to detect the viability of HepG2 cells .DAPI fluorescence staining was performed to observe nucleus morphological changes of HepG2 cells. Western blot analysis was applied to observe the expression of apoptosis-related proteins in HepG2 cells. RESULTS The results showed that GPM could induce HepG2 cells apoptosis and influence HepG2 cells proliferation in a dose-dependent manner. We applied many analysis methods, including differentially expressed genes analysis, Gene Ontology (GO) enrichment analysis, KEGG pathway enrichment analysis, protein-protein interaction network analysis to screen out possible molecular mechanisms. ER-nucleus signaling pathway, cellular response to stress and apoptotic processes were identified the potential anti-cancer molecular biological process of GPM. GPM may also induce apoptosis in HepG2 cells via endoplasmic reticulum stress pathway. The mechanism is closely related to ERs, which might be beneficial for clinical therapy of HCC. CONCLUSION GPM can inhibit cells proliferation and induce apoptosis in HepG2 cells. The gene expression profile of GPM in HepG2 cells was obtained. The present study revealed the potential anti-tumor mechanism of GPM