Lentivirus-Mediated Overexpression of SIVA-1 Reverses Cisplatin Resistance in Gastric Cancer in vitro
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ORIGINAL PAPER
Lentivirus-Mediated Overexpression of SIVA-1 Reverses Cisplatin Resistance in Gastric Cancer in vitro 1
Xiao-Tong Wang
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Lei Li1 Fan-Biao Kong2 Xiao-Gang Zhong1 Wei Mai1 ●
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Received: 9 December 2019 / Accepted: 24 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords SIVA-1 gastric cancer DDP resistance ●
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Introduction Although advances in molecular detection methods have rapidly occurred, the overall prognosis of gastric cancer (GC) remains poor [1, 2]. Currently, surgery and chemoradiotherapy are the main treatment avenues for gastric
These authors contributed equally: Xiao-Tong Wang, Lei Li * Fan-Biao Kong [email protected] * Xiao-Gang Zhong [email protected] * Wei Mai [email protected] 1
Department of Gastrointestinal and Peripheral Vascular Surgery, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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Department of Surgery, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
cancer. Cisplatin (DDP) is a very important chemotherapeutic drug used to treat stomach cancer, and it can inhibit DNA replication and transcription, and induce apoptosis in cancer cells. However, a high number of patients with gastric cancer develop resistance to cisplatin and finally exhibit adverse clinical outcomes [3]. The mechanisms are still controversial. Amable [4] showed that reduction of platinum accumulation and increasing DNA repair activity may be the primary mechanisms related to cisplatin resistance. Moreover, the reduction in ap
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