Abstract
Gastric cancer, as the fifth most frequent disease and the fourth foremost cause of cancer-related death worldwide, remains a main clinical challenge due to its poor prognosis, limited treatment choices, and ability to metastasize. Combining siRNAs to suppress lncRNA with chemotherapeutic medications is a novel treatment approach that eventually increases the therapeutic efficacy of the drug while lessening its adverse effects. This study was performed with the purpose of examining the impact of inhibiting DLGAP1-AS2 expression on gastric cancer cells’ drug chemosensitivity. AGS cells were cultured as the study cell line and were transfected with an optimum dose of DLGAP1-AS2 siRNA and then treated with oxaliplatin. Cell viability was examined using the MTT technique. Apoptosis and cell cycle were evaluated using Annexin V/PI staining and flow cytometry. Later, the scratch test was conducted to investigate the ability of cells to migrate, and the inhibition of the stemness of AGS cells was further investigated through the colony formation method. Finally, the qRT-PCR technique was used to assess the expression of Bax, Bcl-2, Caspase-3, p53, MMP-2, and CD44 genes. The MTT test indicated the effect of gene therapy with siRNA and oxaliplatin in combination reduced the chemotherapy drug dose to 29.92 µM and increased AGS cells’ sensitivity to oxaliplatin. Also, the combination therapy caused a significant increase in apoptosis. However, it reduced the stemness feature, the rate of cell viability, proliferation, and metastasis compared to the effect of each treatment alone; the results also showed the arrest of the cell cycle in the Sub G1 phase after the combined treatment and a further reduction in the number and size of the formed colonies. Suppressing the expression of lncRNA DLGAP1-AS2 by siRNA followed by treatment with oxaliplatin can be utilized as an effective and new therapeutic technique for gastric cancer therapy.
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Acknowledgements
The authors wish to thank the financial support from the National Institute for Medical Research Development (NIMAD) of Iran (project no. 4021422). Also, the authors are thankful for the support of the Immunology Research Center, Tabriz University of Medical Science
Funding
The authors wish to thank the financial support from the National Institute for Medical Research Development (NIMAD) of Iran (project no. 4021422). Also, the authors are thankful for the support of the Immunology Research Center, Tabriz University of Medical Science.
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S.S.A, the first author of the manuscript, performed the experiment, contributed to the cellular and molecular assays, and wrote the manuscript. R.S revised the main text of the manuscript and revised the work critically for important intellectual content. M.A assisted in the cellular and molecular assays and analyzed the data. M.A.H.F revised the main text of the manuscript and revised the work critically for important intellectual content. S.A assisted in the molecular assays. S.N helped with the data categorization and interpreted the results. S.Z.B.M assisted in the cellular assays and revised the main text of manuscript. A.Y and L.N helped with the data categorization and interpreted the results. B.B revised the main text of the manuscript and revised the work critically for important intellectual content. A.A.M, the corresponding author of the manuscript, designed and supervised the project, and revised the main text of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Azadi, S.S., Safaralizadeh, R., Amini, M. et al. Investigating the effect of LncRNA DLGAP1-AS2 suppression on chemosensitivity of gastric cancer to chemotherapy. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03130-7
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DOI: https://doi.org/10.1007/s00210-024-03130-7