NDRG2 promotes adriamycin sensitivity through a Bad/p53 complex at the mitochondria in breast cancer

Chemo-resistance presents a difficult challenge for the treatment of breast cancer. Our previous study showed that N-Myc downstream-regulated gene 2 (NDRG2) is involved in p53-mediated apoptosis induced by chemotherapy, through a mechanism that has so far remained obscure. Here, we explored the role of NDRG2 in chemo-resistance with a focus on Adriamycin (ADR) and found that NDRG2 expression decreased in ADR resistance breast cancer cells. Interestingly, NDRG2 can promote ADR sensitivity by inhibiting proliferation, enhancing cellular damage responses, and promoting apoptosis in a p53-dependent manner. We also found that NDRG2 could upregulate Bad expression by increasing its half-life, which is associated with p53 to mitochondria. Hence, our collective data provided the first evidence that NDRG2 promoting sensitivity of breast cancer is dependent on p53 by preventing p53 from entering the nucleus rather than changing its expression.