3,3′‐Diindolylmethane (DIM) inhibits crosstalk between DU145 prostate cancer cells and THP‐1 monocytes in vitro and in vivo

Abstract

Tumor‐associated macrophages are known to influence neoplastic growth and progression by providing a rich supply of cytokines, proteases, and growth factors. The present study examined the crosstalk between prostate cancer cells and macrophages and whether DIM inhibits these interactions. Our in vitro results revealed that the migration of DU145 cells through collagen‐coated filter paper was markedly increased when THP‐1 cells were co‐cultured in the well under the filter paper. In addition, the DU145 cell‐conditioned medium stimulated the migration of THP‐1 cells. DIM inhibited these migrations of DU145 and THP‐1 cells. The secretion of IL‐6 and IL‐8 were markedly increased when DU145 cells were co‐cultured with THP‐1 cells and DIM inhibited the secretion of these cytokines. Solid tumor growth was markedly accelerated when nude mice were co‐injected with DU145 plus THP‐1 cells compared to DU145 cells alone, and DIM inhibited the tumor growth in mice co‐injected with both cells. Immunohistochemistry of tumor tissues revealed that the expression of CD31 (an endothelial marker), vascular endothelial growth factor, and Ki67 was increased in the co‐inoculation group, which was inhibited by DIM treatment. The present results indicate that interactions between DU145 and THP‐1 cells induce angiogenesis and the migration and growth of these cells and DIM inhibits these effects.