Aim: This study systematically explored the biological effects and mechanisms of PGC on gastric cancer (GC) cells in vitro and in vivo. Method: The critical biological roles of PGC in GC were assessed via EdU staining, Hoechst staining, flow cytometry, mouse models, CCK-8, wound healing, transwell, and sphere-forming assays. The interaction study with IQ-domain GTPase-activating protein 1 (IQGAP1) was used by Liquid chromatography-mass spectrometry co-immunoprecipitation, immunofluorescence staining, CHX-chase assay, MG132 assay, and qRT-PCR. Results: PGC inhibited the proliferation, viability, epithelial–mesenchymal transition, migration, invasion, and stemness of GC cells and promoted GC cell differentiation. PGC suppressed subcutaneous tumor growth and peritoneal dissemination in vivo. The interaction study found PGC inhibits GC cell migration and invasion by downregulating IQGAP1 protein and IQGAP1-mediated Rho-GTPase signaling suppression. In addition, PGC disrupts the stability of the IQGAP1 protein, promoting its degradation and significantly shortening its half-life. Moreover, the expression levels of PGC and IQGAP1 in GC tissues were significantly negatively correlated. Conclusion: PGC may act as a tumor suppressor in the development and metastasis of GC. PGC can downregulate its interacting protein IQGAP1 and inhibit the Rho-GTPase pathway, thereby participating in the inhibition of GC cell migration and invasion.
目的：本研究系统探讨了PGC在体外和体内对胃癌（GC）细胞的生物学效应及其作用机制。方法：通过EdU染色、Hoechst染色、流式细胞术、小鼠模型、CCK-8、划痕愈合、Transwell及成球实验评估PGC在GC中的关键生物学作用。利用液相色谱-质谱联用免疫共沉淀、免疫荧光染色、CHX追踪实验、MG132实验及qRT-PCR技术研究PGC与IQ结构域GTP酶激活蛋白1（IQGAP1）的相互作用。结果：PGC抑制GC细胞的增殖、活力、上皮-间质转化、迁移、侵袭及干性，并促进GC细胞分化。在体内，PGC抑制皮下肿瘤生长和腹膜播散。相互作用研究发现，PGC通过下调IQGAP1蛋白及抑制IQGAP1介导的Rho-GTPase信号通路来抑制GC细胞的迁移和侵袭。此外，PGC破坏IQGAP1蛋白的稳定性，促进其降解并显著缩短其半衰期。同时，GC组织中PGC与IQGAP1的表达水平呈显著负相关。结论：PGC可能在GC的发生发展和转移过程中发挥抑癌作用。PGC可通过下调其相互作用蛋白IQGAP1并抑制Rho-GTPase通路，从而参与抑制GC细胞的迁移和侵袭。
肿瘤(癌症)患者之家