Low-dose Diosbulbin-B (DB) activates tumor-intrinsic PD-L1/NLRP3 signaling pathway mediated pyroptotic cell death to increase cisplatin-sensitivity in gastric cancer (GC)

• DOI: 10.1186/s13578-021-00548-x
• Publication Date: 2021-02-12T20:35:32Z
• Authors: Chunfeng Li; Junqiang Qiu; Yingwei Xue
• Keywords: Homeobox protein NANOG; Viability assay

Abstract Background Emerging evidences suggests that Diosbulbin-B (DB) is effective to improve cisplatin (DDP)-sensitivity in gastric cancer (GC), but its molecular mechanisms were not fully delineated, and this study managed investigate issue. Methods Genes expressions determined by Real-Time qPCR Western Blot at transcriptional translational levels. Cell proliferation viability evaluated cell counting kit-8 (CCK-8) trypan blue staining assay. Annexin V-FITC/PI double assay was used examine apoptosis. The Spheroid formation stemness. xenograft tumor-bearing mice models established, the tumors monitored immunohistochemistry (IHC) employed localization of Ki67 protein tumor tissues. Results Low-dose DB (12.5 μM) downregulated PD-L1 activate NLRP3-mediated pyroptosis, inhibited stem cells (CSCs) properties, sensitize cisplatin-resistant GC (CR-GC) cisplatin. Mechanistically, CR-GC obtained, either low-dose or alone had little effects on cells, while significantly induced apoptotic death treated cells. In addition, triggered pyroptosis co-treated with cisplatin, which abrogated silencing NLRP3. Next, CSCs tended be enriched instead their parental cisplatin-sensitive (CS-GC) spheroid stemness biomarkers (SOX2, OCT4 Nanog) eliminate reversed upregulating programmed ligand-1 (PD-L1). Furthermore, we proved negatively regulated NLRP3 activated pyroptotic downregulating PD-L1. Also, aggravated inhibiting tumorigenesis vivo. Conclusions Collectively, intrinsic PD-L1/NLRP3 pathway cisplatin-sensitivity provided alternative therapy treatments for GC.