RNA-sequencing studies identify genes differentially regulated during inflammation-driven lung tumorigenesis and targeted by chemopreventive agents

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
Xuemin QianFekadu Kassie

Abstract

Chronic pulmonary inflammation has been consistently shown to increase the risk of lung cancer. Therefore, assessing the molecular links between the two diseases and identification of chemopreventive agents that inhibit inflammation-driven lung tumorigenesis is indispensable. Female A/J mice were treated with the tobacco smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and lipopolysaccharide (LPS), a potent inflammatory agent and constituent of tobacco smoke, and maintained on control diet or diet supplemented with the chemopreventive agents indole-3-carbinol (I3C) and/or silibinin (Sil). At the end of the study, mice were sacrificed and tumors on the surface of the lung were counted and gene expression levels in lung tissues were determined by RNA sequencing. The mean number of lung tumors induced by NNK and NNK + LPS was 5 and 15 tumors/mouse, respectively. Dietary supplementation with the combination of I3C and Sil significantly reduced the size and multiplicity (by 50 %) of NNK + LPS-induced lung tumors. Also, we found that 330, 2957, and 1143 genes were differentially regulated in mice treated with NNK, LPS, and NNK + LPS, respectively. The inflammatory response of lung tumors to LPS, as determined by ...Continue Reading

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