Inhibition of interleukin 8/C‑X-C chemokine receptor 1,/2 signaling reduces malignant features in human pancreatic cancer cells.
Abstract
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 sig...Continue Reading
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