Jia Rui-Peng, Xu Lu-Wei, Su Qi, Zhao Jian-Hua, Li Wen-Cheng, Wang Feng, Xu Zheng
Department of Urology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China.
Asian J Androl. 2008 Sep;10(5):758-64. doi: 10.1111/j.1745-7262.2008.00423.x.
To investigate the expression of cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) and the possible mechanism in the development in androgen independent prostate cancer (AIPC).
Immunohistochemistry was performed on paraffin-embedded sections with goat polyclonal against COX-2 and mouse monoclonal antibody against EGFR in 30 AIPC and 18 androgen dependent prostate cancer (ADPC) specimens. The effect of epidermal growth factor (EGF) treatments on the expression of COX-2 and signal pathway in PC-3 and DU-145 cells was studied using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. ELISA was used to measure prostaglandin E2 (PGE2) levels in the media of PC-3 and DU-145 incubated with EGF for 24 h.
COX-2 was positively expressed in AIPC and ADPC, which were predominantly in endochylema of prostate cancer (PCa) cells. Intense staining was seen in AIPC (80%) and in ADPC (55.5%), but there was no significant association between the two groups. EGFR expression was also positive in the two groups (61.8% in ADPC and 90% in AIPC, P < 0.01). A significant association was found between EGFR expression and a higher Gleason score (P < 0.05) or tumor stage (P < 0.05). The expression of PGE2 was increased in PC-3 and DU-145 cells after being incubated with EGF. Both p38MAPK and PI-3K pathway were involved in the PC-3 cell COX-2 upregulation course. In DU-145, only p38MAPK pathway was associated with COX-2 upregulation.
EGFR activation induces COX-2 expression through PI-3K and/or p38MAPK pathways. COX-2 and EGFR inhibitors might have a cooperative anti-tumor effect in PCa.
研究环氧化酶-2（COX-2）和表皮生长因子受体（EGFR）的表达及其在雄激素非依赖性前列腺癌（AIPC）发生发展中的可能机制。
采用免疫组织化学法，用山羊抗COX-2多克隆抗体和小鼠抗EGFR单克隆抗体对30例AIPC和18例雄激素依赖性前列腺癌（ADPC）标本的石蜡包埋切片进行检测。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹分析研究表皮生长因子（EGF）处理对PC-3和DU-145细胞中COX-2表达及信号通路的影响。用酶联免疫吸附测定（ELISA）法检测PC-3和DU-145细胞与EGF孵育24小时后培养基中前列腺素E2（PGE2）的水平。
COX-2在AIPC和ADPC中呈阳性表达，主要位于前列腺癌细胞的胞质内。AIPC组（80%）和ADPC组（55.5%）均可见强染色，但两组之间无显著相关性。两组中EGFR表达也均为阳性（ADPC组为61.8%，AIPC组为90%，P<0.01）。发现EGFR表达与较高的Gleason评分（P<0.05）或肿瘤分期（P<0.05）之间存在显著相关性。PC-3和DU-145细胞与EGF孵育后PGE2表达增加。p38丝裂原活化蛋白激酶（p38MAPK）和磷脂酰肌醇-3激酶（PI-3K）信号通路均参与PC-3细胞COX-2上调过程。在DU-145细胞中，只有p38MAPK信号通路与COX-2上调有关。
EGFR激活通过PI-3K和/或p38MAPK信号通路诱导COX-2表达。COX-2和EGFR抑制剂在前列腺癌中可能具有协同抗肿瘤作用。
