Specifically inhibiting RRM2 causes reduction of invasion and enhances the drug sensitivity to doxorubicin in ER negative breast cancer cells. (A) Western blot analysis showed a decrease in RRM2 caused by siRNA in MDA-MB-231 and ZR-75-1 cells. (B) Decrease of cancer cells invasive ability by RRM2 siRNA. (C) Summary of cancer cell invasion assay. * p < 0.05 in compared with control siRNA (Ctrl siRNA). (D) Assays of cytotoxicity to doxorubicin (DOX) were conducted on MCF-7(ER positive) and MDA-MB-231 (ER negative) cell lines. Both cell lines were seeded and pretreated with or without 10 μM of COH29 for 24 hours, and then cells were treated with different dose of DOX. Each point on the survival curve was normalized to the corresponding value of the initiating point. The sensitivity to doxorubicin was significantly enhanced by the RR inhibitor, COH29, in MDA-MB-231 cells (*p < 0.05), but not in MCF-7 cells.