SIVA-1已显示影响各种不同细胞系的凋亡过程,和SIVA-1显著有助于降低癌细胞对某些化疗药物的反应性。然而,SIVA-1在胃癌中是否有潜在应用尚不清楚.因此,这项研究的目的是阐明SIVA-1在患有胃恶性肿瘤的活体小鼠模型中化疗药物抗性中的独特功能,并初步阐明了潜在的机制。在建立的多药耐药胃癌异种移植小鼠模型中,慢病毒,命名为Lv-SIVA-1,被注射到异种移植肿瘤中,并增加肿瘤中内源性SIVA-1的mRNA和蛋白表达。移植瘤的免疫组织化学检测显示SIVA-1显著上调,SIVA-1的蛋白表达水平高度增加,通过蛋白质印迹检测。此外,我们通过TUNEL检测了SIVA-1在胃癌细胞增殖和细胞凋亡中的作用,发现SIVA-1在体内降低了肿瘤细胞的凋亡并促进了肿瘤的生长。使用实验组和对照组的肿瘤组织之间的TMT测定,检测了差异表达的蛋白质和三种潜在的多药耐药生物标志物(ARF,MDM2和p53)进行了筛选。我们进一步研究了SIVA-1在化疗中起有效作用的分子机制,发现过表达的SIVA-1导致ARF和MDM2表达增加,并抑制了肿瘤组织中p53的表达。总之,SIVA-1在胃肿瘤的多药耐药中起重要作用。此外,过表达的SIVA-1正调节细胞增殖,调整周期进展,并以ARF/MDM2/p53依赖性方式降低对胃癌药物治疗的反应。这项新的研究通过调节SIVA-1的表达为胃癌的化学管理提供了基础。
SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (
ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased
ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an
ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.