HBXIP regulates etoposide-induced cell cycle checkpoints and apoptosis in MCF-7 human breast carcinoma cells
HBXIP regulates etoposide-induced cell cycle checkpoints and apoptosis in MCF-7 human breast carcinoma cells
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HBXIP 调节依托泊苷诱导的 MCF-7 人乳腺癌细胞的细胞周期检查点和细胞凋亡
DOI：
10.1016/j.gene.2018.01.019
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发表时间：
2018-03-20
期刊：
影响因子：
3.5
通讯作者：
Wang, Feng-ze
中科院分区：
文献类型：
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作者：
Fei, Hong-rong;Li, Zhao-jun;Wang, Feng-ze
依托泊苷是一种抗癌DNA拓扑异构酶II类毒物，在人类癌症的治疗中发挥着重要作用。不幸的是，许多癌症对依托泊苷产生耐药性，对化疗没有反应，导致治疗困难和预后不良。在本研究中，我们研究了HBXIP基因沉默对MCF-7人乳腺癌细胞对依托泊苷化疗敏感性的影响。我们发现依托泊苷增加了HBXIP在MCF-7细胞中的表达，并促进了HBXIP向细胞核的动员。敲除HBXIP可减轻依托泊苷诱导的G2/M期和S期阻滞。在HBXIP基因敲除细胞中，依托泊苷处理后p53和p21的上调被减弱。此外，HBXIP基因沉默使依托泊苷诱导的细胞凋亡和MCF-7细胞中caspase-9和PARP的裂解变得敏感。RNAi下调HBXIP的表达可阻断依托泊苷激活的ERK和Akt。这些结果表明，HBXIP可以调节MCF-7细胞株对依托泊苷的敏感性，并进一步暗示HBXIP是人类乳腺癌的靶点。
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.