Doxorubicin is widely used in chemotherapeutic regimen primarily for its conventional direct tumoricidal activity, however, to our knowledge, the data from this study provide the first evidence that PGE2 secreted by Doxorubicin-resistant tumor cells can promote the expansion and polarization of MDSCs via upregulating their endogenous miR-10a expression, and the activation of cAMP/PKA and EP4/AMPK signaling pathway play pivotal roles in this activity. The gene discussed is PTGER4; the disease is neoplasm.