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[FZD5在小鼠前列腺癌骨转移中的作用及作用机制]

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

作者信息

Zhang Xiao, Mo Qi-wang

出版信息

Zhonghua Nan Ke Xue. 2016 Feb;22(2):128-32.

PMID:26939396
Abstract

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 proliferation 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 silencing 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.

摘要

目的

探讨FZD5基因在前列腺癌骨转移中的作用机制,并寻找针对该疾病的新治疗方法。

方法

我们测定了前列腺癌PC3细胞中FZD5基因的表达水平,在将小干扰RNA(siRNA)转染入PC3细胞并使FZD5基因沉默后,观察细胞迁移和增殖的变化。我们通过向裸鼠胫骨注射前列腺癌细胞建立前列腺癌骨转移模型。然后向小鼠胫骨注射对照siRNA和FZD5沉默的siRNA,在注射后0、1和3周通过X线成像评估肿瘤诱导的骨破坏情况,并在注射后3周进行苏木精-伊红(HE)染色。

结果

将FZD5沉默的siRNA转染入前列腺癌PC3细胞后,FZD5基因的表达降低了约70%。基因沉默组的细胞增殖率明显低于对照组(P<0.05),在FZD5沉默后48小时,该组细胞迁移率与后一组相比下降了30%(P<0.05)。向小鼠胫骨注射对照siRNA或FZD5沉默的siRNA后3周,两组均观察到溶骨性破坏,不过FZD5沉默组较轻,仅可见少数残留骨小梁。

结论

沉默FZD5基因可降低前列腺癌细胞的迁移和增殖,有助于抑制骨转移和骨破坏,从而提高患者的生存率和生活质量。

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