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.

SIVA-1 在许多不同细胞系的细胞凋亡诱导中发挥着关键作用，并参与顺铂 (DDP) 介导的抗肿瘤作用机制。然而，SIVA-1在胃癌顺铂耐药中的作用尚未被揭示。为了探讨SIVA-1对DDP耐药的影响，构建重组pGV358-GFP-SIVA-1慢病毒载体，并转染人顺铂耐药MKN45/DDP胃癌细胞。随后，在 MKN45/DDP 细胞中建立了稳定的 SIVA-1 过表达，这导致 MKN45/DDP 细胞体外 DDP 敏感性增加。流式细胞术表明，与对照相比，SIVA-1 过表达增加了凋亡细胞的百分比。集落形成测定清楚地表明，SIVA-1 过表达后细胞生长和增殖受到显着抑制。此外，SIVA-1的过表达抑制了MKN45/DDP细胞的体外迁移和侵袭潜力。 Western blot 分析表明，SIVA-1 增加了 p53、p73 和 p14ARF 的表达水平，而降低了 Bcl-2、MDM2 和 Bcl-xL 的表达。简而言之，SIVA-1 在体外上调 p53、p73 和 p14ARF 的蛋白表达，并降低 Bcl-2、MDM2 和 Bcl-xL 的蛋白表达，随后逆转胃癌细胞中的顺铂耐药性，表明 SIVA-1 可以作为减轻化疗耐药性的一个有价值的潜在目标。