Up regulation of IL-6 is involved in di (2-ethylhexyl) phthalate (DEHP) induced migration and invasion of non small cell lung cancer (NSCLC) cells

Di (2-ethylhexyl) phthalate (DEHP), which is widely used in polyvinyl chloride materials, can be easily accumulated into human body. Lung cancer cells can be directly exposed to DEHP via inhalation, however, the effects and related mechanisms of DEHP on the progression of non small cell lung cancer (NSCLC) were not illustrated. Our present study revealed that DEHP less than 10-4M had no significant effect on the proliferation of A549 or H1299 cells, while nanomolar DEHP can trigger the migration and invasion of NSCLC cells. DEHP treatment also increased the expression of interleukin-6 (IL-6) and IL-8. Silencing of IL-6, while not IL-8, can attenuate DEHP induced migration and invasion of NSCLC cells. This was confirmed by result that neutralization antibody of IL-6, while not anti-IL-8, attenuated DEHP induced invasion of A549 cells. The inhibitor of NF-κB, while not ERK1/2 or Akt, abolished DEHP induced up regulation of IL-6 and invasion of NSCLC cells. DEHP treatment can increase the phosphorylation, nuclear localization, and transcriptional activities of p65, one of the major parts of NF-κB complex. Collectively, our study revealed that DEHP can stimulate NSCLC migration and invasion via NF-κB mediated up regulation of IL-6.