Role of NF-κB activation in hormone-refractory prostate cancer

点击翻译按钮获取中文摘要

Establishment of xenograft models using prostate cancer cell lines and osteblastic cell linesXenograft models using LNCaP, MDA-PCa2b and LNCaP mixed with MC3T3-E1cells were established on dorsal subcutaneous lesion of nude mice.Assessment of the expression of NF-κB, androgen receptor, and SRC-3 by immunohistochemical studyXenograft samples and clinical prostate samples obtained from patients with hormone-naive or hormone-refractory prostate cancer were used for immunohistochemical analysis. NF-κB mainly showed cytoplasmic expression in both xenografts and any stage of clinical prostate cancer. Less than 20% of cancer cells showed nuclear NF-κB expression in these samples. Higher gleason grade tumors had higher percentage of positivity of nuclear NF-κB expression.Expression levels of androgen receptor and SRC-3 in clinical prostate cancer were correlated.The effect of prostate cancer on oeteoclastgenesisCrude conditioned medium (CM) from LNCaP, DU145, PC3 and MDA PCa2b cells enhanced mRNA for receptor activator of NF-κB ligand (RANKL) in MC3T3-E1cells. However, these CM did not affect osteoprotegerin (OPG) mRNA expression in MC3T3-E1cells. CM from LNCaP, DU145 cells also enhanced maturation of osteoclast precursor cells (Cancer letter, in press).Serum levels of IL-6, TGF-β1, IL8 and VEGF in patients with hormone-refractory prostate cancerAfter disease progression, serum IL-6 levels significantly elevated, whereas serum TGF-β1 levels significantly declined. Higher serum IL-6 levels had significant association with poor prognosis, whereas higher serum TGF-β1 levels did not. After disease progression, serum IL-8 and VEGF levels increased marginally.The effect of NF-κB inhibitor, MG132, on prostate cancer growthA proteosomal inhibitor, MG132, inhibits the activation of NF-κB. MG132 inhibited the growth of LNCaP, DU145 and PC3 cells significantly in vitro.