Blocking IL-6/GP130 Signaling Inhibits Cell Viability/Proliferation, Glycolysis, and Colony Forming Activity in Human Pancreatic Cancer Cells

Background: Elevated manufacture of the professional-inflammatory cytokine interleukin-6 (IL-6) and disorder of IL-6 signaling promotes tumorigenesis and therefore are connected with poor survival outcomes in multiple cancer types. Recent reports demonstrated the IL-6/GP130/STAT3 signaling path plays a pivotal role in pancreatic cancer development and maintenance.

Objective: We try to develop effective treatments through inhibition of IL-6/GP130 signaling in pancreatic cancer.

Methods: The results on cell viability and cell proliferation were measured by MTT and BrdU assays, correspondingly. The results on glycolysis was resolute by cell-based assays to determine lactate levels. Protein expression changes were evaluated by western blotting and immunoprecipitation. siRNA transfection was utilized to knock lower oestrogen receptor a gene expression. Colony developing ability was resolute by colony developing cell assay.

Results: We shown that IL-6 can induce pancreatic cancer cell viability/proliferation and glycolysis. We demonstrated that the repurposing Food and drug administration-approved drug bazedoxifene could hinder the IL-6/IL-6R/GP130 complexes. Bazedoxifene also inhibited JAK1 binding to IL-6/IL-6R/GP130 complexes and STAT3 phosphorylation. Additionally, bazedoxifene impeded IL-6 mediated cell viability/ proliferation and glycolysis in pancreatic cancer cells. Consistently, other IL-6/GP130 inhibitors SC144 and evista demonstrated similar inhibition of IL-6 stimulated cell viability, cell proliferation and glycolysis. In addition, the 3 IL-6/GP130 inhibitors reduced the colony developing ability in pancreatic cancer cells.

Conclusion: Our findings shown that IL-6 stimulates pancreatic cancer cell SC144 proliferation, survival and glycolysis, and supported persistent IL-6 signaling is a practicable therapeutic target for pancreatic cancer using IL-6/GP130 inhibitors.