HBXIP regulates etoposide-induced cell cycle checkpoints and apoptosis in MCF-7 human breast carcinoma cells.

Etoposide, an anticancer DNA topoisomerase II poison, plays an important role in the therapy for human cancers. Unfortunately, many cancers develop etoposide resistance and do not respond to chemotherapy, leading to difficulty in treatment and poor prognosis. In this study, we investigate the effects of HBXIP gene silencing on etoposide chemosensitivity in MCF-7 human breast cancer cells. We find that etoposide increases HBXIP expression and promotes mobilization of HBXIP to the nucleus in MCF-7 cells. Knockdown of HBXIP alleviates etoposide-induced G2/M or S phase arrest. Upregulation of p53 and p21 upon etoposide treatment is attenuated in HBXIP knock-down cells. Moreover, HBXIP gene silencing sensitizes etoposide-induced cell apoptosis and cleavage of caspase-9 and PARP in MCF-7 cells. Knockdown of HBXIP expression by RNAi abrogates the etoposide-activated ERK and Akt. These results indicate that HBXIP can modulate the etoposide sensitivity of MCF-7 cell lines and further implicate HBXIP as a target for human breast cancer.