Role of RKIP in regulating the expression of MMPs in invasion and metastasis of prostate cancer
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摘要: 目的:研究Raf激酶抑制蛋白(RKIP)通过调控基质金属蛋白酶(MMPs)的表达对前列腺癌细胞侵袭转移的作用,探讨其作用机制。方法:收集正常癌旁组织及恶性前列腺癌组织,免疫组化法测体内前列腺癌组织中RKIP的表达;通过质粒转染建立RKIP过表达及沉默C4-2B细胞系,设为RKIP过表达组和RKIP沉默组,并设置对照组,细胞迁移实验及侵袭实验测3组细胞迁移及侵袭情况,RT-PCR法测3组细胞中MMP-1 mRNA、MMP-2 mRNA、MMP-9 mRNA表达情况。结果:良性组RKIP的表达水平高于恶性组(P<0.05);RKIP沉默组单个视野内迁移及侵袭的平均细胞数目及细胞中MMP-1 mRNA、MMP-2 mRNA、MMP-9 mRNA的表达水平均高于对照组和RKIP过表达组,其中对照组上述指标均高于RKIP过表达组(P<0.05)。结论:RKIP不仅在体内抑制前列腺癌的发生,在体外也可抑制前列腺癌细胞的转移与侵袭,且其作用机制可能是通过对MMP-1、MMP-2、MMP-9进行负调控,此发现可为前列腺癌的早期诊断,预后评估以及靶向治疗等提供新的研究思路及指导意义。Abstract: Objective: To study the role of Raf kinase inhibitor protein(RKIP) in regulating the expression of matrix metalloproteinase(MMPs) in invasion and metastasis of prostate cancer, and explore its mechanism. Method: We collected the normal para-carcinoma and malignant prostate cancer tissue, and the expression of RKIP in prostate cancer tissue was detected by immunohistochemistry. RKIP overexpression and silencing C4-2 B cell lines were established by plasmid transfection. The cells were divided into RKIP overexpression group and RKIP silencing group, and the control group was set up. Cell migration and invasion were measured in three groups. The expressions of MMP-1, MMP-2 and MMP-9 in three groups were detected by RT-PCR. Result: The expression of RKIP in benign group was higher than that in malignant group(P<0.05). The average number of migration and invasion cell in one single view, the mRNA expressions of MMP-1, MMP-2 and MMP-9 in RKIP silencing group were higher than those in control group and RKIP overexpression group, and the above indexes in control group were higher than those in RKIP overexpression group(P<0.05).Conclusion: RKIP could inhibit the occurrence of prostate cancer in the body, besides RKIP could inhibit migration and invasion of prostate cancer cell in vitro, and its mechanism may be negative control of MMP-1, MMP-2, MMP-9. This finding provides a new research idea and the instructed significance for the early diagnosis, assessment of prognosis and target therapy of prostate cancer.
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Key words:
- prostate cancer /
- metastasis /
- invasion /
- RKIP /
- MMPs
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