Zhou Jialin, Zheng Fucun, Dai Peng
Wuhan Vocational College of Software and Engineering, Wuhan Open University, Wuhan, 430205, Hubei, People's Republic of China.
Wuhan Bo Ruiheng Pharmaceutical Technology Co. Ltd., Wuhan, 430200, Hubei, People's Republic of China.
Discov Oncol. 2025 May 14;16(1):761. doi: 10.1007/s12672-025-02481-8.
Gastric cancer (GC) is a prevalent malignancy of gastrointestinal tract with a high incidence worldwide. Polydatin, a bioactive compound in Polygonum cuspidatum, possesses antitumor effects. We aimed to study the role of polydatin in GC and its possible mechanism. HGC27 cells were treated with varying doses of polydatin, and cell viability was tested by CCK-8 assay. Colony formation assay and immunofluorescence staining of Ki67 were employed to evaluate the proliferation of HGC27 cells. Sphere formation assay was conducted to analyze the stemness of HGC27 cells and levels of genes related to stemness was tested by RT-qPCR and immunoblotting. Additionally, angiogenesis was assessed by performing tube formation assay and examining VEGF secretion. Then, histone deacetylase 7 (HDAC7) was upregulated in polydatin-treated HGC27 cells to explore the regulatory effect of polydatin on HDAC7. Results suggested that polydatin gradually reduced the viability and suppressed the proliferation of HGC27 cells with the increase of polydatin concentrations. Notably, polydatin dose-dependently decreased sphere formation in size, accompanied by downregulated SOX2 and OCT4 levels. Besides, the conditioned medium from polydatin treated HGC27 cells resulted in decreased VEGF secretion levels and tube formation capacities. Importantly, Super-PRED database and molecular docking predicted that HDAC7 was a downstream target that could combine with polydatin. Bioinformatics analysis indicated that HDAC7 expression was elevated in GC tissues and high HDAC7 expression predicted low prognosis. Moreover, polydatin downregulated HDAC7 expression in HGC27 cells. Particularly, HDAC7 upregulation blocked the influences of polydatin on proliferation, stemness and angiogenesis of HGC27 cells. Collectively, polydatin inhibits the stemness and angiogenesis of GC cells by targeting down-regulation of HDAC7.
胃癌（GC）是一种常见的胃肠道恶性肿瘤，在全球范围内发病率很高。虎杖苷是虎杖中的一种生物活性化合物，具有抗肿瘤作用。我们旨在研究虎杖苷在胃癌中的作用及其可能的机制。用不同剂量的虎杖苷处理HGC27细胞，并通过CCK-8法检测细胞活力。采用集落形成试验和Ki67免疫荧光染色评估HGC27细胞的增殖。进行成球试验分析HGC27细胞的干性，并通过RT-qPCR和免疫印迹检测与干性相关的基因水平。此外，通过进行管腔形成试验和检测VEGF分泌来评估血管生成。然后，在经虎杖苷处理的HGC27细胞中上调组蛋白去乙酰化酶7（HDAC7），以探讨虎杖苷对HDAC7的调节作用。结果表明，随着虎杖苷浓度的增加，虎杖苷逐渐降低HGC27细胞的活力并抑制其增殖。值得注意的是，虎杖苷剂量依赖性地减小成球大小，同时SOX2和OCT4水平下调。此外，经虎杖苷处理的HGC27细胞的条件培养基导致VEGF分泌水平和管腔形成能力降低。重要的是，Super-PRED数据库和分子对接预测HDAC7是一个可以与虎杖苷结合的下游靶点。生物信息学分析表明，HDAC7在胃癌组织中表达升高，HDAC7高表达预示着预后不良。此外，虎杖苷下调HGC27细胞中HDAC7的表达。特别是，HDAC7上调阻断了虎杖苷对HGC27细胞增殖、干性和血管生成的影响。总的来说，虎杖苷通过靶向下调HDAC7来抑制胃癌细胞的干性和血管生成。
