Bass Robert, Perry Billy, Langenstroer Peter, Thrasher J Brantley, Dennis Katie L, Tawfik Osama, Holzbeierlein Jeffrey
Department of Urology, University of Kansas Hospital, Kansas City, Kansas 66160, USA.
J Urol. 2009 Feb;181(2):615-9; discussion 619-20. doi: 10.1016/j.juro.2008.10.029. Epub 2008 Dec 16.
We explored the molecular correlates of the effect of finasteride on prostate tissue in patients undergoing radical prostatectomy.
Patients undergoing radical prostatectomy for localized prostate cancer were eligible for study. After providing informed consent patients were randomized to receive 5 mg finasteride or placebo daily for at least 30 days before surgery. At surgery prostate tissue was harvested from the surgical specimen and sent for analysis. Tissue samples were analyzed for the pro-apoptotic factors caspase-3, caspase-7 and IGFBP-3. Samples were also analyzed for the tumor suppressor/proto-oncoproteins bcl-2, p53 and p21. Finally, tissues were analyzed for androgen receptor density and insulin growth factor-1.
A total of 22 study and 20 placebo samples were collected and analyzed. Negligible staining for bcl-2 or caspase-3 was noted in each group. Statistical differences were not observed for bcl-2, p53, p21 or insulin growth factor-1 between the groups. There was a statistically significant difference in caspase-7 and IGFBP-3. A mean of 77% and 99.9% of cells stained for caspase-7 in the treatment and placebo groups, respectively (p = 0.007). In 3 patients caspase-7 staining disappeared completely and it was decreased by 70% and 50% in 1 patient each. Mean intensity staining for IGFBP-3 was 1.03 in the treatment group and 1.54 in the placebo group (p = 0.005). The staining intensity of nuclear androgen receptors on benign and cancerous cells was not significantly different between the treatment and placebo groups. However, there was a significant difference in androgen receptor staining between benign and cancer cells in the 2 populations. Mean nuclear androgen receptor staining intensity in all cancer and all benign tissue samples was 119.3 and 151.8, respectively (0.001).
Finasteride administered 30 days before surgery appears to decrease the apoptotic factors caspase-7 and IGFBP-3 in cancer cells, while having little to no effect on caspase-3, insulin growth factor-1, bcl-2, p53 and p21. This short-term study may have interesting implications for interpreting Prostate Cancer Prevention Trial data on the molecular level. No differences were noted between the treatment and placebo groups in the expression of nuclear androgen receptor. However, decreased expression of androgen receptors was present in cancer cells compared to that in benign prostate cells in the 2 groups.
我们探讨了非那雄胺对接受根治性前列腺切除术患者前列腺组织影响的分子关联因素。
因局限性前列腺癌接受根治性前列腺切除术的患者符合研究条件。在获得知情同意后，患者被随机分组，在手术前至少30天每天接受5毫克非那雄胺或安慰剂治疗。手术时，从手术标本中获取前列腺组织并送去分析。组织样本分析促凋亡因子半胱天冬酶-3、半胱天冬酶-7和胰岛素样生长因子结合蛋白-3。样本还分析肿瘤抑制因子/原癌蛋白bcl-2、p53和p21。最后，分析组织中的雄激素受体密度和胰岛素生长因子-1。
共收集并分析了22份研究样本和20份安慰剂样本。每组中bcl-2或半胱天冬酶-3的染色均不明显。两组之间bcl-2、p53、p21或胰岛素生长因子-1未观察到统计学差异。半胱天冬酶-7和胰岛素样生长因子结合蛋白-3存在统计学显著差异。治疗组和安慰剂组中分别有平均77%和99.9%的细胞半胱天冬酶-7染色阳性（p = 0.007）。3例患者半胱天冬酶-7染色完全消失，另外各有1例患者染色分别减少70%和50%。治疗组胰岛素样生长因子结合蛋白-3的平均染色强度为1.03，安慰剂组为1.54（p = 0.005）。治疗组和安慰剂组良性和癌细胞上核雄激素受体的染色强度无显著差异。然而，这两组人群中良性和癌细胞之间雄激素受体染色存在显著差异。所有癌组织和所有良性组织样本中核雄激素受体的平均染色强度分别为119.3和151.8（p = 0.001）。
术前30天给予非那雄胺似乎可降低癌细胞中的促凋亡因子半胱天冬酶-7和胰岛素样生长因子结合蛋白-3，而对半胱天冬酶-3、胰岛素生长因子-1、bcl-2、p53和p21几乎没有影响。这项短期研究可能对在分子水平解释前列腺癌预防试验数据具有有趣的启示。治疗组和安慰剂组在核雄激素受体表达方面未发现差异。然而，与两组中的良性前列腺细胞相比，癌细胞中雄激素受体表达降低。
