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Lentivirus-Mediated Overexpression of SIVA-1 Reverses Cisplatin Resistance in Gastric Cancer in vitro

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Abstract

SIVA-1 plays a critical role in the induction of apoptosis in a number of different cell lines and participates in the mechanism of cisplatin (DDP)-mediated antitumor effects. However, the involvement of SIVA-1 in cisplatin resistance in gastric carcinoma has not been revealed. To explore the effect of SIVA-1 on DDP resistance, a recombinant pGV358-GFP-SIVA-1 lentiviral vector was constructed and transfected into human cisplatin-resistant MKN45/DDP gastric cancer cells. Subsequently, stable SIVA-1 overexpression was established in MKN45/DDP cells, which resulted in increased DDP sensitivity in MKN45/DDP cells in vitro. Flow cytometry demonstrated that SIVA-1 overexpression increased the percentage of apoptotic cells compared to that in the control. The colony formation assay clearly revealed that cell growth and proliferation were significantly suppressed following SIVA-1 overexpression. In addition, overexpression of SIVA-1 inhibited the migratory and invasive potential of MKN45/DDP cells in vitro. Western blot analysis indicated that SIVA-1 increased the expression levels of p53, p73, and p14ARF, whereas it reduced Bcl-2, MDM2, and Bcl-xL expression. In short, SIVA-1 upregulated the protein expression of p53, p73, and p14ARF and decreased that of Bcl-2, MDM2, and Bcl-xL in vitro and subsequently reversed cisplatin resistance in gastric cancer cells, suggesting that SIVA-1 serves as a valuable potential target for attenuating chemotherapy resistance.

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All data were generated and analyzed by the corresponding author. All the data and materials are available from X.T.W. and F.B.K.

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Acknowledgements

We appreciate Mrs. Qiao-Ming Deng and Mrs. Chang Wang for their great contribution to the family. Natural Science Foundation of China (No. 81660416).

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X.T.W., L.L., F.B.K., X.G.Z., and W.M. produced the figures, tables, and references. X.T.W. and L.L. contributed equally to this work.

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Correspondence to Fan-Biao Kong, Xiao-Gang Zhong or Wei Mai.

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Wang, XT., Li, L., Kong, FB. et al. Lentivirus-Mediated Overexpression of SIVA-1 Reverses Cisplatin Resistance in Gastric Cancer in vitro. Cell Biochem Biophys 78, 455–463 (2020). https://doi.org/10.1007/s12013-020-00929-y

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