Mechanisms by Which Interleukin-6 Attenuates Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

Abstract EN

Interleukin-6, a multifunctional cytokine, contributes to tumor cell proliferation and differentiation.

However, the biological mechanisms that are affected by the expression of interleukin-6 in bladder cancer cells remain unclear.

We evaluated the effects of interleukin-6 expression in human bladder carcinoma cells in vitro and in vivo.

The results of interleukin-6-knockdown experiments in T24 cells and interleukin-6-overexpression experiments in HT1376 cells revealed that interleukin-6 reduced cell proliferation, migration, and invasion in vitro.

Xenograft animal studies indicated that the overexpression of interleukin-6 downregulated tumorigenesis of bladder cells and that interleukin-6 knockdown reversed this effect.

The results of RT-PCR, immunoblotting, and reporter assays indicated that the overexpression of interleukin-6 upregulated the expression of the mammary serine protease inhibitor (MASPIN), N-myc downstream gene 1 (NDRG1), and KAI1 proteins in HT1376 cells and that interleukin-6 knockdown reduced the expression of these proteins in T24 cells.

In addition, results of immunoblotting assays revealed that interleukin-6 modulated epithelial-mesenchymal transitions by upregulating the expression of the E-cadherin, while downregulation N-cadherin and vimentin proteins.

Our results suggest that the effects of interleukin-6 on the regulation of epithelial-mesenchymal transitions and the expressions of the MASPIN, NDRG1, and KAI1 genes attribute to the modulation of tumorigenesis in human bladder carcinoma cells.