It was demonstrated that double silencing of KHDRBS3 and cDENND4C or silencing of cDENND4C and overexpression of miR-577 significantly increased the apoptosis rate of U87 glioma cells induced by Dox, compared with the silencing of KHDRBS3, cDENND4C, or overexpression of miR-577 alone, suggesting that the treatment of KHDRBS3, cDENND4C, and miR-577 alone or in combination could enhance the antitumor effect of Dox by promoting its penetrating capability across BTB. This evidence concerns the gene KHDRBS3 and central nervous system cancer.