DNA methylation of DKK3 modulates docetaxel chemoresistance in human nonsmall cell lung cancer cell.

Dickkopf-related protein 3 (DKK3) gene, as a tumor suppressor gene, has been discovered in various cancers, but its relationship with tumor chemoresistance is still unclear. In this study, this laboratory detected that DNA methylation contributes to the downregulation of DKK3 in docetaxel resistance of human lung cancer cells and its possible biochemical mechanism. DKK3 has been proved to be downregulated by hypermethylation in docetaxel-resistant lung cancer cells. Upregulation of DKK3 can reverse the chemoresistance of docetaxel-resistant cell lines in vitro by growth inhibition and enhancement of apoptosis. Conversely, downregulation of DKK3 could induce parental human lung cancer cells insensitivity to docetaxel by promoting proliferative capacity and inhibiting apoptosis of cancer cells. In addition, the authors observed that overexpression of DKK3 might decrease the expression of P-glycoprotein. All results suggested that epigenetic downregulation of DKK3 leads to docetaxel resistance in human nonsmall cell lung cancer (NSCLC) cells by increased expression of P-glycoprotein. DKK3 may reveal a novel molecular target for docetaxel resistance for NSCLC patients in the future.