• Novel 3D bioengineered tumor scaffolds with different stiffness were developed. • Cells with different LOX expression levels were used to generate tumor tissue. • DECM scaffold has good cytocompatibility. • DECM with high stiffness promotes the resistance of MDA-MB-231 cells to cisplatin. • DECM with high stiffness increases the expression of Bcl-2 and ABCB1.