转录因子HBP1通过诱导前列腺癌细胞凋亡增强放射敏感性

Yicheng Chen, Yueping Wang, Yan-lan Yu, Liwei Xu, You-yun Zhang, Shicheng Yu, Gonghui Li, Zhigeng Zhang
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引用次数: 8

摘要

前列腺癌放疗近年来逐步开展;然而,一些患者在放疗后经常出现获得性放射耐药。HBP1 (HMG-box转录因子1)是一种转录抑制剂,可抑制数十种癌基因的表达。在我们之前的研究中,我们发现HBP1的表达水平与前列腺癌的转移和预后密切相关,但HBP1与前列腺癌放射耐药的关系在很大程度上是未知的。本研究通过对前列腺癌患者的临床资料进行比较,发现前列腺癌近距离放疗疗效与HBP1基因表达水平呈正相关。通过对前列腺癌细胞的体外研究,我们发现HBP1表达水平与癌基因表达水平呈负相关。此外,HBP1过表达可使前列腺癌细胞对辐射敏感,增加前列腺癌细胞的凋亡。此外,采用动物模型分析HBP1基因与体内前列腺癌放射敏感性的关系;结果表明,敲低HBP1基因可降低异种移植物对辐射的敏感性。这些研究发现了前列腺癌放射敏感性的特定分子机制,这表明HBP1是前列腺癌放疗的新靶点。
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Transcription Factor HBP1 Enhances Radiosensitivity by Inducing Apoptosis in Prostate Cancer Cell Lines
Radiotherapy for prostate cancer has been gradually carried out in recent years; however, acquired radioresistance often occurred in some patients after radiotherapy. HBP1 (HMG-box transcription factor 1) is a transcriptional inhibitor which could inhibit the expression of dozens of oncogenes. In our previous study, we showed that the expression level of HBP1 was closely related to prostate cancer metastasis and prognosis, but the relationship between HBP1 and radioresistance for prostate cancer is largely unknown. In this study, the clinical data of patients with prostate cancer was compared, and the positive correlation was revealed between prostate cancer brachytherapy efficacy and the expression level of HBP1 gene. Through research on prostate cancer cells in vitro, we found that HBP1 expression levels were negatively correlated with oncogene expression levels. Furthermore, HBP1 overexpression could sensitize prostate cancer cells to radiation and increase apoptosis in prostate cancer cells. In addition, animal model was employed to analyze the relationship between HBP1 gene and prostate cancer radiosensitivity in vivo; the result showed that knockdown of HBP1 gene could decrease the sensitivity to radiation of xenograft. These studies identified a specific molecular mechanism underlying prostate cancer radiosensitivity, which suggested HBP1 as a novel target in prostate cancer radiotherapy.
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