PHD2 exerts anti-cancer and anti-inflammatory effects in colon cancer xenografts mice via attenuating NF-κB activity

In this study, the effects of PHD2 in colon cancer were evaluated, and the underlying molecular mechanisms were investigated. The results showed that overexpressing PHD2 exerted proliferative and migratory inhibition in colon cancer cells. The expression of cell cycle and epithelial-mesenchymal transition (EMT)-associated proteins were changed: CyclinD1, CDK4, N-cadherin, and Vimentin were down-regulated, while E-cadherin was up-regulated in PHD2-overexpressing colon cancer cells. Moreover, in colon cancer xenograft mice, PHD2 overexpression suppressed tumor growth accompanied by decreased Ki67 expression. Importantly, we further demonstrated that overexpressing PHD2 attenuated inflammation in colon cancer xenograft mice through weakening accumulation of myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (TAMs), as well as secretions of pro-inflammatory cytokines including G-CSF, TNF-α, IL-6, IL-8, IL-1β, and IL-4. Mechanistically, PHD2 overexpression obviously suppressed NF-κB activity through decreasing phosphorylated IκB-α while increasing cytoplasmic NF-κB p65 levels in colon cancer. Our findings support the anti-cancer and anti-inflammatory roles of PHD2 and offer a preclinical proof of tumor progression regulated by cancer cells and inflammation.
Source: Life Sciences - Category: Biology Source Type: research

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