Objective To investigate the prevention effects of new type 5α reductase inhibitor-dutasteride on human PC-3 cells transplanting tumors in nude mice and explore its mechanism. Methods Human prostate cancer cells PC-3 were transplanted subcutaneously around 30 nude mice’s necks to establish transplanting tumor models. Then 30 nude mice were divided randomly and evenly into the dutasteride group(treated with intraperitoneal injection of dutasteride serum), the fenasteride group(treated with intraperitoneal injection of fenasteride serum) and the control group (treated with intraperitoneal injection of no durg serum). The tumor growth curve, tumor double time and tumor formation rate were measured during 30 days administration . The immunochemistry and MIAS image analysis were applied to investigate ECM degradation and RT-PCR was applied to measure the expression of integrin β1, and β6 after 30 days of transplantation.Results The tumor growth curves of three groups were similar. Dutasteride could prolong tumor double time as compared with the other 2 groups but there was no statistical significance (P>0.05). Both dutasteride and fenasteride could degrade tumor ECM by inhibiting the expression of CL and FN (P<0.01 or P<0.05), and enhancing MMP-2 expression (P<0.01 or P<0.05) compared with the control group. Dutasteride could inhibit integrin β1 and β6 expression (P<0.01 or P<0.05) and had the inhibiting trend of integrin β2 (P>0.05) compared with the control group. Conclusion Dutasteride can inhibit ECM-integrin signal pathway by degrading ECM and inhibiting the expression of integrinβ1 and β6. Even so, it can only prolong the tumor formation and double time but can not prevent the formation of human PC-3 transplanting tumor in nude mice. Thus the present data can not supportthat dutasteride has the prevention effect on PCa, but reflecting the complicatedprinciples of PCa formation.%目的：探讨新型5α还原酶抑制剂--度他雄胺对人前列腺癌PC-3细胞裸鼠移植瘤的成瘤预防效应与机制。方法选取BALB/C裸鼠30只，随机平均分为度他雄胺组、非那雄胺对照组和阴性对照组，均采用皮下注射人前列腺癌PC-3细胞建立移植瘤模型，同时度他雄胺组裸鼠每日腹腔注射度他雄胺含药血清，非那雄胺组每日腹腔注射非那雄胺含药血清，阴性对照组每日腹腔注射非含药血清。给药30d内，观察实验期间各组动物移植瘤生长曲线，移植瘤倍增时间，成瘤百分率。30d后处死动物，免疫组化法结合图像分析各组裸鼠瘤体ECM降解程度， RT-PCR法检测细胞外基质-整合素（ECM-integrin）跨膜信号通路关键蛋白integrinβ1，β2和β6的表达情况。结果实验期间各组裸鼠移植瘤成瘤率均为100%，移植瘤生长曲线近似，与阴性对照组相比，度他雄胺和非那雄胺组移植瘤成瘤平均潜伏期延长（P＜0.05），度他雄胺组肿瘤倍增时间比阴性对照组和非那雄胺组延长，差异具均统计学意义（P ＜0.05）。免疫组化检测度他雄胺组和非那雄胺组瘤体ECM较阴性对照组明显降解，表现为纤维链接蛋白（FN）和胶原（CL）表达明显降低（P ＜0.01或P ＜0.05），基质金属蛋白酶-2（MMP-2）表达明显增强（P ＜0.01或P ＜0.05）；RT-PCR法检测度他雄胺组瘤体细胞integrinβ1和β6表达较阴性对照组明显降低（P ＜0.01或P ＜0.05），integrinβ1表达较非那雄胺组降低（P＜0.05），结论度他雄胺能通过降解人前列腺PC-3细胞裸鼠抑制瘤ECM，降低integrinβ1和β6表达，从而抑制决定前列腺癌细胞生长、增殖和转移的关键信号通路-ECM-integrin信号通路，从而延长移植瘤成瘤和倍增时间，但不能有效抑制成瘤率，因此尚不能明确其具有预防前列腺癌的作用，同时也说明前列腺癌形成和生长机制具有多重复杂性。
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