FZD5在小鼠前列腺癌骨转移中的作用机制研究

Role and action mechanisms of FZD5 in prostate cancer bone metastasis in mice

目的:探讨FZD5基因在前列腺癌骨转移中的作用机制,寻找前列腺癌骨转移的新的治疗方法。方法:检测前列腺癌PC3细胞内FZD5基因表达水平。将siRNA转染入PC3细胞后使FZD5基因沉默,继而观察PC3细胞迁移、增殖的变化。在此基础上通过小鼠胫骨注射建立前列腺癌骨转移模型,之后每周在胫骨腔内注射对照siRNA或FZD5基因沉默siRNA,于0、1和3周拍X平片观察肿瘤骨破坏,在3周后取材,行HE染色观察肿瘤骨破坏情况。结果:将FZD5基因沉默siRNA转染入前列腺癌PC3细胞后,细胞内FZD5基因表达量下降约70%。基因沉默组细胞增殖显著低于对照组(P<0.05)。FZD5基因沉默48 h后,细胞迁移能力较对照组下降了30%(P<0.05)。小鼠模型胫骨腔内注射对照siRNA或沉默siRNA 3周时,对照组和实验组均可见溶骨性破坏,但FZD5基因沉默组破坏相对较少,仍可见部分残留骨小梁。结论:通过抑制FZD5基因,可减少前列腺癌细胞的迁移和增殖,可能辅助减少前列腺癌患者的骨转移及骨破坏,从而提高患者的生存率及生活质量。其从分子生物学的角度为前列腺癌的发病机制以及治疗方法提供了新的思路。

Objective： To investigate the action mechanisms of the FZD5 gene in prostate cancer bone metastasis and search for some new treatments for this disease. Methods ： We determined the expression level of the FZD5 gene in prostate cancer PC3 cells and, after transfection of siRNA into the PC3 cells and silence of the FZD5 gene, observed the changes in the migration and prolifera- tion of the cells. We established the model of prostate cancer bone metastasis by tibial injection of prostate cancer cells in the nude mice. Then we injected control siRNA and FZD5-silenced siRNA into the tibia of the mice followed by evaluation of tumor-induced bone destruction by X-ray imaging at 0, 1, and 3 weeks and by HE staining at 3 weeks after injection. Results ： After transfection of FZD5-silenced siRNA into the prostate cancer PC3 cells, the expression of the FZD5 gene was decreased about 70%. The rate of cell proliferation was significantly lower in the gene silencing group than in the control （ P 〈 0.05 ）, and that of cell migration dropped by 30% in the former as compared with the latter group at 48 hours after FZD5 silencing （ P 〈 0.05 ）. At 3 weeks after injection of control siRNA or FZD5-silenced siRNA into the tibia of the mice, osteolytic damage was observed in both groups, though less in the FZD5 si- lencing group, with only a few remaining bone trabeculae visible. Conclusion： Silencing the FZD5 gene can reduce the migration and proliferation of prostate cancer cells, help to suppress bone metastasis and destruction, and thereby improve the survival rate and quality of life of the patients.