Abstract
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.
Highlights
Prostate cancer is very common in western countries, the incidence of which ranks first in male cancers [1]
All patients underwent the implantation of 125iodine (125I) particles according to the guidelines of American Society for Radiation Oncology (ASTRO) and American College of Radiology (ACR)
The expression level of HBP1 gene in blood samples was detected via RT-PCR in 66 patients who received radiotherapy and compared to preradiation control samples
Summary
Prostate cancer is very common in western countries, the incidence of which ranks first in male cancers [1]. Radical prostatectomy was preferred clinically for localized prostate cancer of early stage and low-risk patients [4], while for late stage, intermediate- and highrisk patients, androgen deprivation therapy has been used [5]. In the last 20 years in western countries, radiotherapy (including EBRT and permanent radioactive seed implantation) for the treatment of prostate cancer has gradually replaced the radical prostatectomy and androgen deprivation therapy and has become one of the main methods for the treatment of prostate cancer [6, 7]. Studies that focus on the reduction of prostate cancer cell resistance and promote increased tumor cell sensitivity to radiotherapy treatment are predominant in prostate cancer
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