Li Feng, Pascal Laura E, Zhou Jianhua, Zhou Yibin, Wang Ke, Parwani Anil V, Dhir Rajiv, Guo Peng, He Dalin, Nelson Joel B, Wang Zhou
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an, Shaanxi, China.
Department of Urology, University of Pittsburgh School of MedicinePittsburgh 15232, PA, USA.
Am J Clin Exp Urol. 2018 Feb 5;6(1):1-10. eCollection 2018.
The mechanisms involved in the development of benign prostatic hyperplasia (BPH) are poorly understood. One potential mechanism involved in BPH pathogenesis may involve altered expression of genes related to apoptosis and proliferation because reduced cell death and increased proliferation are thought to contribute to prostatic enlargement. This study examined the expression of B-cell lymphoma 2 (BCL-2) and B-cell lymphoma-extra large (BCL-XL), two important anti-apoptosis factors that are also capable of inhibiting cell proliferation via accelerated G1 arrest or delayed G1/S transition, using immunostaining in simple prostatectomy BPH specimens from patients naïve to androgen manipulation. Since androgens and inflammation are thought to play important roles in BPH pathogenesis, we tested the effect of inhibiting 5a-reductase and/or COX-2 on the expression of BCL-2 and BCL-XL in BPH specimens from prostate cancer patients with BPH. These patients had no prior use of chronic NSAIDs and/or 5a-reductase inhibitors and were treated with celecoxib, finasteride, celecoxib plus finasteride or no treatment for 28 consecutive days prior to surgery. In all specimens, BCL-2 and BCL-XL staining was evident in both luminal and basal epithelial cells, with more intense staining in basal cells. Both luminal and basal cells exhibited decreased BCL-2 and BCL-XL staining in BPH nodules compared to the surrounding normal prostatic tissues. In prostate cancer patients with BPH, celecoxib and/or finasteride did not affect the expression of BCL-2 and BCL-XL in luminal or basal cells in BPH nodules and normal adjacent tissues. These results suggest that BCL-2 and BCL-XL may act as anti-proliferative factors in BPH pathogenesis, and the effect of celecoxib and/or finasteride on BPH is unlikely mediated through modulating BCL-2 and BCL-XL signaling.
良性前列腺增生（BPH）发展过程中涉及的机制目前尚不清楚。BPH发病机制中一个潜在的机制可能涉及与细胞凋亡和增殖相关基因的表达改变，因为细胞死亡减少和增殖增加被认为会导致前列腺增大。本研究使用免疫染色法检测了B细胞淋巴瘤2（BCL-2）和B细胞淋巴瘤-超大（BCL-XL）的表达，这两种重要的抗凋亡因子也能够通过加速G1期停滞或延迟G1/S期转换来抑制细胞增殖，检测对象为未接受过雄激素处理的单纯前列腺切除术BPH标本。由于雄激素和炎症被认为在BPH发病机制中起重要作用，我们测试了抑制5α-还原酶和/或COX-2对前列腺癌合并BPH患者BPH标本中BCL-2和BCL-XL表达的影响。这些患者既往未使用过慢性非甾体抗炎药和/或5α-还原酶抑制剂，在手术前连续28天接受塞来昔布、非那雄胺、塞来昔布加非那雄胺治疗或不治疗。在所有标本中，BCL-2和BCL-XL染色在管腔和基底上皮细胞中均明显可见，基底细胞中的染色更强。与周围正常前列腺组织相比，BPH结节中的管腔和基底细胞均表现出BCL-2和BCL-XL染色减少。在前列腺癌合并BPH的患者中，塞来昔布和/或非那雄胺不影响BPH结节和相邻正常组织中管腔或基底细胞中BCL-和BCL-XL的表达。这些结果表明，BCL-2和BCL-XL可能在BPH发病机制中作为抗增殖因子发挥作用，塞来昔布和/或非那雄胺对BPH的作用不太可能通过调节BCL-2和BCL-XL信号传导来介导。
