ADH1B Gene Promotes Gastric Cancer Tumorigenesis and its Cisplatin Resistance through the EMT Pathway

Background: Cisplatin resistance significantly affects the outcome of gastric can-cer treatment. In this study, genes associated with cisplatin resistance were investigated and discussed. Methods: We analyzed the sequencing data of GSE14208 patients from the GEO database us-ing differential and enrichment analyses. Gastric cancer cells with high ADH1B expression and low ADH1B expression were selected by qPCR and WB to construct ADH1B overexpress and silence cells. The optimal cisplatin concentrations for treatment were determined via CCK-8 detection and WB. Furthermore, we assessed drug resistance, cellular activity, and in-vasion and migration capacities using IC50, CCK-8 assays, Transwell, and migration tests. Apoptosis was evaluated using flow cytometry and EDU staining. The pathway influenced by ADH1B was examined through WB and immunofluorescence. The impact of gene expression on the tumorigenic potential of gastric cancer cells was assessed by analyzing tumor size, mass, and histology in HE-stained tumor sections and Ki67 and protein pathway immuno-histochemistry in a mouse tumorigenesis model. Results: This study revealed that ADH1B may exhibit a cancer-promoting effect, according to our database analysis, and is associated with drug resistance. Silencing ADH1B in AGS cells led to a reduced IC50, as well as decreased viability, invasion, and migration capabilities while increasing apoptosis rates. Conversely, overexpressing ADH1B in MKN-45 cells re-versed these effects. Western blot and immunofluorescence results indicated that the expres-sion levels of proteins involved in the EMT, PI3K, and MAPK pathways were altered follow-ing the silencing and overexpression of ADH1B. Moreover, silencing ADH1B not only re-duced tumor volume and weight but also enhanced the tumor-reducing effects of cisplatin, as evidenced by changes in tumor structure; overexpression had the opposite effects. The altera-tions in pathway protein expression in tumor sections mirrored those observed in cells. Conclusion: This study identified the gene ADH1B as a critical factor in the incidence and drug resistance of gastric cancer. It was demonstrated through cellular and tumorigenic assays that ADH1B promotes carcinogenesis and enhances cisplatin resistance in gastric cancer cells via the EMT signaling pathways. result: In this study, we screened the ADH1B gene, the expression of ADH1B was different in different gastric cancer cells, the sensitivity of different gastric cancer cells to Cisplatin was different, and the expression of ADH1B in gastric cancer cells treated with different concentrations of Cisplatin was also changed. Gastric cancer cells overexpressing ADH1B showed enhanced cell function, decreased apoptosis level and weakened sensitivity to Cisplatin. Gastric cancer cells overexpressing ADH1B had weaker cell function, higher apoptosis level, and were more sensitive to Cisplatin, while gastric cancer cells overexpressing ADH1B had weaker cell function, higher apoptosis level, and were more sensitive to Cisplatin. The change of ADH1B expression also affects the expression of EMT-related markers and resistance-associated pathway proteins. In mouse in vivo experiments, ADH1B expression also affected tumor growth and Cisplatin efficacy in mice.