Interactions between
interleukin (IL)-8 and its receptors, C‑X-C
chemokine receptor 1, (CXCR1) and CXCR2 serve crucial roles in increasing
cancer progression. Inhibition of this signaling pathway has yielded promising results in a number of human
cancers, including breast,
melanoma and colon. However, the effects of CXCR1/2 antagonist treatment on
pancreatic cancer remain unclear. The present study aimed to demonstrate that treatment with the clinical grade CXCR1/2 antagonist,
reparixin, or the newly discovered CXCR1/2 antagonist,
SCH527123, may result in a reduction of the malignant features associated with this lethal
cancer. The effects of
reparixin or
SCH527123 exposure on human
pancreatic cancer cell lines BxPC‑3, HPAC, Capan‑1, MIA PaCa‑2, and AsPC‑1 were examined in regard to cell proliferation, cell viability, colony formation and migration. The effects of CXCR1/2 inhibition on the
protein expression of well-known downstream effectors, including phosphorylated (p)-signal transducer and activator of transcription 3 (STAT3), p‑RAC‑α
serine/threonine-protein kinase (p‑AKT), p‑extracellular signal-regulated
kinase (p‑ERK1/2) and p‑ribosomal
protein S6 (p‑S6), were assessed by western blotting assays. The effects of IL‑8 signaling on the proliferative activities intrinsic to the human
pancreatic cancer cell lines Capan‑1, AsPC‑1 and HPAC were examined by
bromodeoxyuridine assay. Treatment with either
reparixin or
SCH527123 yielded dose-dependent growth suppressive effects on HPAC, Capan‑1 and AsPC‑1 cells that may have otherwise undergone robust proliferation upon IL‑8 stimulation. In addition,
reparixin or
SCH527123 treatment inhibited CXCR1/2-mediated signal transduction, as demonstrated by the decreased phosphorylation levels of effector molecules STAT3, AKT, ERK and S6 that are downstream of the IL‑8/CXCR1/2 signaling cascade in HPAC cells. These data were in close agreement with the reduced cell migration and colony formation. Results from the present study suggested that
reparixin and
SCH527123 may be promising therapeutic agents for the treatment of
pancreatic cancer by inhibiting the IL‑8/CXCR1/2 signaling cascade.